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INFKCTini'S  DISEASES 


THEIR  ETIOLOGY,  DIAGNOSIS,  AM)  TREATMENT 


BY 


G.  ii.  j*<><;  ee 

PROFESSOR    EXTRAORDINARY    IN   rilfr'u  II.TV   OF   MKIilMSK  OK   PARI* 

MEMBER  OF  THE    BIOI.OUICAL  SOCIETY 

PHYSICIAN   TO  THE   HOSPITAL  OF   POKTE   I>'  AT  I'.l.l:  \  I  I.I  II  I:- 


TRANSLATED   BY 

M.   S.   GABRIEL,  M.I). 

ILLUSTRATED    WITH     FORTY-THREE    ENGRAVINGS 


LEA    BROTHERS   &   CO. 

N  E  \Y    Y  0  R  K    AND    PHIL  A  D  E  LPHI  A 
1903 


Enten-d  according  to  the  Act  of  Congress,  in  the  year  1903,  by 

LEA    BROTHERS     &    CO., 
in  the  Office  of  the  Librarian  of  Congress.     All  rights  reserved. 


I)  O  B  N  A  N  ,     PRINTKR. 


PREFACE. 


Those  members  of  the  profession  who  confine  their  reading  to 
English  alone  will    welcome  this  translation  of  Professor  Roger'fi 
great  work.     His  subject  comprehends  almost  the  entire  BCO] 
internal  medicine  and  touches  many  of  the  principles  underlying 
modern  surgery  as  well. 

During  the  last  decades  the  marvellous  discoveries  in  pathology 
have  succeeded  one  another  with  such  bewildering  rapidity  that 
time  has  apparently  been  lacking  for  the  assimilation  of  the  newly 
acquired  knowledge;  and,  as  a  result,  many  have  failed  to  corre- 
late the  new  theories  with  the  old  facts.  The  effect  of  the  present 
volume  is  to  harmonize  any  seeming  antagonism  between  experi- 
mental research  and  clinical  observation,  and  to  reduce  the  theories 
of  infection  and  immunity  to  the  basis  of  practical  utility. 

This  material  could  not  have  been  prepared  by  a  laboratory 
investigator  however  brilliant,  nor  by  a  clinician  however  pro- 
found his  experience,  nor  yet  could  it  have  been  the  product  of 
collaboration:  its  creation  remained  for  one  who  combined  the 
instincts  and  training  of  a  student  at  home  in  original  research 
with  almost  unprecedented  opportunities  for  clinical  investigation. 
Possessed  of  an  equal  facility  in  each.  Professor  Roger  has  pursued 
clinical  and  experimental  researches  jointly,  although  he  always 
subordinates  the  latter  to  the  former  and  never  loses  sight  of  the 
fact  that  the  purpose  of  the  laboratory  is  to  amplify  and  explain 
clinical  observations,  to  the  end  that  from  both  the  therapist  should 
receive  information  indispensable  to  practical  results. 

With  the  directness  of  the  true  philosopher,  the  author  unfolds 
his  subjects  by  using  the  simplest  methods.      He  first  studies  the 


iv  PREFACE. 

pathogenic  agents,  inquires  into  their  distribution  in  nature,  the 

conditions  under  which  they  attack  man,  and  their  mode  of  inva- 
sion. Full  consideration  is  then  given  to  their  influence  upon 
the  human  economy  and  the  reaction  of  the  latter  upon  the  in- 
vaders. Heredity,  predisposition,  and  immunity  receive  specific 
and  general  attention,  while  to  the  more  directly  practical  depart- 
ments of  diagnosis,  prognosis,  and  treatment,  both  preventive  and 
curative,  ample  time  and  space  are  devoted. 

While  the  reading  of  no  page  may  be  omitted  without  loss,  it 
is  desired  to  direct  special  attention  to  the  author's  consideration 
of  the  influence  of  infection  upon  the  various  organs  of  the  body 
— his  researches  in  experimental  appendicitis,  pseudotuberculosis, 
variola,  and  the  vesicatory  test;  also  to  his  admirable  treatment 
of  the  pathology  of  fevers  and  the  defenses  of  the  organism  against 
infections.  The  final  chapters,  comprising  more  than  a  quarter 
of  the  volume,  are  devoted  to  a  masterly  discussion  of  the  thera- 
peutics of  infectious  diseases. 

As  a  basis  for  his  opinions  in  the  matter  of  treatment,  as  well 
as  the  clinical  observations  reflected  throughout  the  work,  Pro- 
fessor Roger  has  had  recourse  to  the  opportunities  afforded  him 
at  the  Hotel  Dieu  and  the  isolation  wards  in  the  hospital  of  Porte 
d'Aubervilliers.  In  these,  the  latter  of  which  receives  all  cases 
of  contagious  diseases  occurring  in  Paris,  he  personally  attended 
over  ten  thousand  patients  during  a  period  of  five  years. 

The  author  knows  his  subject  thoroughly,  and,  like  a  strong 
man  rejoicing  in  his  strength,  he  takes  a  keen  delight  in  grappling 
with  its  problems.  No  doubt  many  readers  will  join  him  in  this 
pleasure  and  thereby  become  stronger  men. 


(1 0  N  T  K  N  T  S 


CH  A  !'  I  E  l:    I  . 
General  Considerations .17 

CHAPTER    II. 
General  Characters  of  Pathogenic  Bacteria      .        .  .      43 

CHAPTER   III. 
Etiology  of  Infections     ......... 

CHAPTEE    IV. 

Pathogenesis  of  Infections     ........ 

CHAPTER    V. 
Microbic  Associations .    135 

CHAPTER   VI. 

Defenses  and  Reactions  of  the  Organism    ...... 

CHAPTER    VII. 
Suppuration 

CHAPTER   VIII. 
Gangrene    .         .         .         .         .         .         .         .         .         .         .         .         .225 

CHAPTER    IX. 
Septicemias  and   Pyemias  .         .         . -44 

CHAPTER    X. 
Nodular  Infections  .         .         .         .         .         .         .         .         .         .272 

CHAPTER    XI 
Cellular  Degenerations  .........     323 


vj  CONTENTS. 

•   11  a  PTER   XII. 

PAGF. 

General  Reactions  -Fbveh 333 

CHAPTER   XIII. 
Influence  of   1mm  riONS  upon  Various  Parts  of  the  Organism        .     359 

CHAPTER   XIV. 
Influence  of  Infection  upon  the  Various  Parts  of  the  Organism 

tinned) 402 

CHAPTER   XV. 
Influence  of  Infection  upon  the  Various   Parts  of  the  Organism 

{Continued) 442 

CHAPTER    XVI. 
Influence  of  Infection-  cjpon  the  Various  Parts  of  the  Organism 

(Concluded) 469 

CHAPTER    XVII. 
Evolution  of  Infectious  Diseases 494 

CHAPTER    XV  III. 
The  Conseqi  en<  es  of  Infection 541 

CHAPTER    XIX. 
Mechanism  of  Immunits   and  of  Predisposition     .  .     551 

CHAPTER    XX. 
Congenital  Infection-  and  Heredity •     580 

CHAPTER   XXI. 
Diagnosis  and  Prognosis  of  Infectious  Diseases  .  .     606 

CHAPTER   XXII. 
Therapeutics  of  Infectious  Diseases     ...  ...     642 

CHAP  T  E  R   XXIII. 
Therapeutics  of  Infectious  Diseases  (Concluded)  .  ■  757 

CHAPTER    XXIV. 
Hygiene  and  Prophylaxis  of  Infectious  Diseases  .        .        ■    837 


INFECTIOUS   DISEASES. 


CHAPTER   I. 

GENERAL  CONSIDERATIONS. 

Definition  of  Infectious   Diseases.      The   Artificial    Limits  of   thi-   (iroup.       Transition 
between  Infectious  and   Parasitic  Diseases.     Classification  of    infectious  I' 
Historical.     Ancient  Views  of  Infections.     Analogy  between    Infections   and 
mentations.      Researches  upon  the  Animate  Agents  of  Infections.      The  Patho- 
genic   Bacteria.      Pathogenic    Plants    and  Animals.      Classification  of    Infectious 
Agents. 

Definition.  The  term  "infection"  is  one  of  those  words  which  are 
most  frequently  employed  in  medicine  and  of  which  the  meaning  has 
been  most  notably  modified  by  time.  While  it  was  well  defined  by 
the  ancients,  it  is  employed  by  modern  authors  without  any  attempt 
to  designate  the  precise  meaning  attributed  to  it  at  the  present  day. 

To  the  ancients  "infection''  meant  everything  that  contaminates 
the  air.1  From  the  time  of  Lucretius,  Ovid,  and  Virgil  until  the  days  i  if 
Copland,  the  word  was  employed  in  this  sense.  The  same  idea  was 
expressed  by  Dupuytren,  who  believed  that  the  cause  of  infection 
resided  in  the  action  exerted  upon  the  air  by  people  crowded  into 
low,  narrow,  dark,  and  dirty  localities,  and  by  decaying  vegetable 
or  animal  substances.  The  air,  when  contaminated  by  such  emana- 
tions, becomes  a  true  toxic  agent. 

It  was  only  at  a  recent  date  that  an  attempt  was  made  to  differ- 
entiate infection  from  contagion.2  The  two  definitions  proposed  by 
De  la  Berge,  Monneret,  and  Fleury  in  their  compendium3  give  a 
clear  idea  of  the  conceptions  prevailing  in  the  first  half  of  the  nine- 
teenth century. 

1  Infection,  from  Latin  infcctionan,  infcctus.  infect,  or  more  exactly,  impregnated: 
in,  jaccrc,  to  make  in,  to  put  in. 

2  Contagion,  contagio,  from  cum,  tangerc,  to  touch.  This  term  is  applied  to  diseases 
which  originate  by  contact. 

3  Compendium  de  med.  pratique.  1S37.  vol.  ii.  p.  463;  vol.  v.  p.  167,  1S42. 


18  INFECTIOUS  DISEASES. 

"Infection."'  they  say,  "is  the  mode  of  propagation  of  certain 
diseases  which  depend  upon  the  toxic  or  morbific  action  exerted  by 
decaying  vegetable  or  animal  substances  and  the  miasms  exhaled  by 
the  healthy  or  diseased  human  body  upon  one  or  several  individuals 
placed  under  conditions  which  render  them  particularly  susceptible 
to  their  influence. 

"Contagion  is  that  mode  of  propagation  of  disease  by  which  an 
afflicted  individual  communicates  the  malady  to  others  favorably 
situated  to  receive  it,  and  the  latter,  in  their  turn,  become  agents  of 
propagation  of  the  disease  the  characters  of  which  remain  identical 
throughout." 

It  is  interesting  to  note  that  in  the  foregoing  two  definitions  the 
authors  admit  the  necessity  of  morbid  opportunity  for  the  genesis 
of  infectious  and  contagious  diseases — a  conception  that  has  been 
fully  confirmed  by  recent  researches.  On  the  other  hand,  the  con- 
tagious diseases  which  are  always  reproduced  with  the  same  char- 
acters belong  to  what  are  at  present  designated  as  infectious  diseases. 
It  is  to  be  noted,  however,  that  in  passing  from  one  individual  to 
another,  the  disease  does  not  always  preserve  its  primitive  character. 
Erysipelas,  for  instance,  may  engender  puerperal  fever.  The  defini- 
tion of  infections  is  still  less  successful,  for  it  is  applicable  to  a  great 
variety  of  morbid  states  due  to  intoxications.  This  confusion  is 
encountered  even  in  recent  works.  Several  processes  that  are  in 
reality  to  be  attributed  to  autointoxication  have  been  described 
under  the  name  of  autoinfection. 

It  is  thus  evident  that,  toward  the  middle  of  the  nineteenth  cen- 
tury, the  diseases  transmitted  through  the  agency  of  air — i.  e.,  mias- 
matic diseases — were  considered  as  infectious  and  were  clearly  dis- 
tinguished from  those  conveyed  by  contact,  either  mediate  or  imme- 
diate.1 The  limits  of  infections,  however,  were  soon  to  be  widened. 
The  miasmatic  diseases  were  classed  with  those  arising  from  inocu- 
lation or  absorption  of  decaying  organic  substances.  The  group  of 
autoinfections  were  thus  created  and  included  the  two  great  processes 
which  are  still  designated  as  purulent  and  putrid  infection. 

We  are  thus  brought  to  the  present  time,  when  investigators  seeking 
for  the  causes  of  these  miasmatic  diseases,  putrid  and  purulent, 
demonstrated  the  intervention  of  microscopic  animate  agents.  These 
animate  agents  were  first  discovered  in  the  air,  and  the  miasmatic 

1  Chomel.     El&nents  de  path.  g<Sn<5rale,  Paris,  1863,  5th  ed.,  p.  38. 


GENERA  L  CONSIDER  A  TIONB.  1  !i 

theory  thus  received  experimental  sanction.    Next,  thi  fre- 

quently seen  lo  vegetate  upon  our  integumente  and  mucous  mem- 
branes, and  the  theory  of  autoinfection  was  established  upon  an 
unassailable  basis. 

From  that  time  infectious  diseases  were  naturally  considered  to 
be  always  dependent  upon  some  animate  agent.  They  constitute  a 
particular,  autonomous  group  in  the  class  of  parasitic  disea 

Agreement  upon  this  point  is  unanimous.  Difficulty  arises,  how- 
ever, when  an  attempt  is  made  to  learn  the  distinctive  characters 
separating  infection  from  parasitism.  The  clinical  symptom-,  ol 
course,  are  not  comparable.  No  one  would  consider  as  infectious  the 
manifestations  caused  by  taenia  or  the  slight  dermatitis  excited  by 
miorosporon  furfur.  Nevertheless,  considerable  embarrassment  is 
experienced  when  accurate  definitions  are  to  be  formulated.  Hence, 
most  authors  have  avoided  offering  any,  depending  upon  the  ability 
of  the  reader  to  comprehend  what  they  were  incapable  of  defining. 

In  view  of  these  difficulties,  some  authors  sought  the  character- 
istics of  infection  in  the  agents  generating  the  morbid  manifestations, 
and  proposed  to  reserve  the  name  infectious  for  diseases  depending 
upon  the  action  of  bacteria,  To  the  author  this  view  does  not  seem 
acceptable.  It  is  impossible  to  make  etiological  and  pathogenic  con- 
ceptions the  exclusive  basis  of  a  classification.  The  nosographer 
must,  first  of  all,  weigh  the  various  reactions  of  the  organism,  viz., 
the  symptoms  presented  by  the  patient:  he  must  start  from  the 
disturbances  observed  during  life  and  proceed  from  the  apparent 
phenomena  to  the  hidden  cause. 

The  ancient  physicians  succeeded  in  individualizing  typhoid  fever, 
anthrax,  glanders,  leprosy,  and  tuberculosis  by  the  attentive  study 
of  symptoms.  Pathological  anatomy  completed  the  work  begun  by 
clinicians.  Modern  researches  in  etiology  have  added  little  to  ancient 
conceptions  and,  in  the  majority  of  instances,  have  confirmed  them. 
Laennec's  genius  established  the  unity  of  tuberculosis  merely  through 
the  data  furnished  by  clinical  observation  and  macroscopic  anatomy. 
The  histological  researches  of  Grancher  and  Thaon  confirmed  Laen- 
nec's conception.  Koch's  discovery,  completing  Yillemin's  work, 
furnished  an  unassailable  basis  for  ancient  ideas.  It  did  no  more 
than  permit  the  recognition  of  the  tubercular  character  oi  some  less 
clearly  defined  lesions  of  minor  importance. 

Clinical  observation  did  not  require  the  assistance  of  bacteriology 
in  describing  the  eruptive  fevers.    Nothing  is  better  established  than 


20  IXFECTIO  US  DISEASES. 

this  part  of  medicine.  Mediate  or  immediate  contagion,  regular  or 
irregular  types,  malignant  or  benign,  early  or  belated  complications, 
all  had  been  observed  by  the  older  physicians,  and  it  is  hardly  prob- 
able that  the  discovery  of  the  agents  giving  rise  to  these  infections 
will  greatly  modify  the  ancient  descriptions. 

Should  bacteriological  research  be  taken  as  an  exclusive  basis  it 
would  lead  to  the  separation  of  certain  diseases  which  clinical  obser- 
vation seems  to  have  rightly  classed  together.  Paludism  is  the  most 
characteristic  type  of  miasmatic  infections.  It  is  produced,  not  by 
bacteria,  but  by  animal  parasites — protozoa.  Accordingly,  it  should 
be  excluded  from  the  group  of  infections,  a  step  which  no  observer 
would  approve.  The  same  is  true  also  of  smallpox,  varicella,  and 
vaccinia,  provided,  as  numerous  investigations  tend  to  prove,  we 
admit  that  they  are  due  to  animal  parasites.  Nevertheless,  by  their 
symptomatic  and  contagious  characters,  they  head  the  list  of  infec- 
tious diseases. 

The  study  of  tuberculosis  and  actinomycosis  furnishes  fresh  con- 
firmation for  our  view.  Clinical  observers  had  noted  strong  analogies 
between  these  two  diseases.  Bacteriology  widened  the  breach  sepa- 
rating them.  One  of  them,  tuberculosis,  was  classed  among  the 
infections,  since  it  depends  upon  a  bacillus ;  the  other,  actinomycosis, 
was  included  with  parasitic  diseases,  as  it  is  due  to  an  algae  whose 
organization  is  far  more  complex.  Recent  researches,  however,  tend 
to  justify  the  clinical  view  by  establishing  a  close  relationship,  at 
first  unsuspected,  between  the  two  pathogenic  agents.  The  infective 
agent  of  tuberculosis  seems  to  have  unduly  occupied  a  place  among 
the  bacilli.  Under  certain  conditions  this  plant  presents  prolonga- 
tions, ramifications,  and  swellings:  it  assumes  the  aspect  of  actino- 
myces,  and,  like  it,  enters  into  the  group  of  streptothrix  or  oospora. 
Additional  inquiry  has  thus  established  an  etiological  analogy  cor- 
responding to  symptomatic  analogy.  If,  however,  bacterial  diseases 
alone  should  be  considered  as  infectious,  tuberculosis  would  have  to 
be  excluded  from  the  group  of  infections.  If,  on  the  other  hand, 
tuberculosis  should  be  retained  in  that  group,  then  actinomycosis 
should  also  be  assigned  a  like  position;  and  there  remains  no  reason 
why  those  diseases  which  are  caused  by  a  certain  species  of  asper- 
gillus  or  certain  yeasts  should  not  be  placed  in  the  same  category. 

Abandoning  etiological  classification,  some  authors  have  chosen 
pathogenesis  as  a  basis.  A  disease  should  be  called  infectious  or 
parasitic,  according  to  the  mode  of  action  of  the  cause.    In  the  former 


< ;  /<;  N  /<;  ft  A  L  co  N8  WEBATIO  ss.  2 1 

case  the  morbific  agenl  acts  by  the  soluble  substances  which  it 
secretes;  in  the  latter  instance  its  action  is  merely  a  mechanical  one 

— some  form  of  I riiiiiii.-iiisin  inflicted  upon  the  tissues. 

Such  a  conception  is  better.  It  would  be  perfect  if  we  knew  with 
greater  accuracy  the  mode  of  action  of  the  pathogenic  agents.  At 
any  rate,  this  pathogenic  classification  docs  not  differ  greatly  from 
symptomatic  classifications,  which  I  prefer,  [f  the  reactions  pre- 
sented by  diseased  organisms  arc  of  the  same  nature,  the  reason  is 
that  the  mode1  of  action  of  the  agents  calling  them  into  play  are 
analogous.  Classifications  based  upon  pathogenesis  are,  however, 
hardly  possible  as  yet.  Too  much  obscurity  and  discord  still  prevail 
in  this  branch  of  medicine.  It  is,  therefore,  better  to  rely  upon  the 
symptoms  presented  by  the  sick.  This  method  is  simpler  and,  it 
seems  to  the  writer,  even  more  rational.  For  the  philosopher  as  well 
as  for  the  practitioner,  a  classification  must  be  founded  upon  observ- 
able and  not  upon  hidden  signs.  "We  observe  the  morbid  dis- 
turbances, the  clinical  manifestations,  and  their  study  enables  us  to 
discover  the  lesions  which  accompany  them,  the  causes  which  pro- 
duce them,  and  the  mechanism  which  accounts  for  them. 

What,  then,  are  the  clinical  characters  which  will  enable  us  to 
recognize  the  infectious  nature  of  a  disease? 

In  many  instances  it  is  possible  to  ascertain  the  contagious  nature 
and  epidemic  progress  of  a  disease;  but  this  is  not  sufficient  to  prove 
its  infectious  character.  Certain  nervous  affections  are  contagious  and 
epidemic.  The  history  of  insanity  and  hysteria  furnishes  numerous 
illustrations  of  this.  The  distinction  is,  as  a  rule,  easy,  though  not 
always.  It  was  long  believed  that  the  contagiousness  of  whooping- 
cough  was  due  to  nervous  influence — some  sort  of  imitation.  To-day 
it  is  known  that  there  is  actual  transmission  of  a  living  germ.  The 
difficulty  is  as  great  with  regard  to  intoxications.  Poisoning  is 
at  times  epidemic  or  endemic,  the  affected  individuals  having  ab- 
sorbed nearly  equal  amounts  of  noxious  substances.  In  infections, 
particularly  in  those  of  aquatic  origin,  the  study  of  etiological  con- 
ditions shows  that  the  pathogenic  agent  was  imponderable,  and 
that  it  must  have  increased  by  reproduction  within  the  organism, 
which  fact  demonstrates  its  animate  nature.  The  surgical  or  puer- 
peral septicemias  transmitted  through  insufficiently  cleansed  instru- 
ments or  hands  are  of  this  nature. 

In  order  that  animate  agents  may  develop  and  give  rise  to  dis- 
turbances, a  certain  length  of  time  must  elapse  between  their  intro- 


22  INFECTIO  US  DISEASES. 

duction  into  the  system  and  the  appearance  of  the  first  morbid 
reactions.  This  is  the  period  of  incubation.  It  properly  belongs  to 
infectious  and  parasitic  diseases.  In  practice,  however,  it  is  often 
impossible  to  distinguish  the  incubation  period  from  the  period  of 
latency  observed  under  a  great  number  of  circumstances,  notably 
in  intoxications  and,  at  times,  also  in  nervous  reactions. 

When  the  microbe  is  sufficiently  developed  the  organism  reacts 
by  two  orders  of  manifestations,  namely,  local  and  general.  The 
local  reactions  cannot  serve  to  characterize  infection,  for  they  appear 
in  many  parasitic  diseases,  and  also  in  various  intoxications.  The 
general  reactions,  including  fever,  are  likewise  observed  in  poison- 
ings, in  autointoxications — gout,  for  example. 

Thus,  taken  separately,  each  of  the  characters  of  infection  presents 
nothing  special.  We  must,  therefore,  acknowledge  the  singular 
genius  of  the  early  observers  who,  in  the  midst  of  analogous  etio- 
logical conditions  and  comparable  symptomatic  manifestations, 
were  able  to  classify  the  infectious  processes.  Modern  researches 
have  in  almost  every  instance  confirmed  the  results  of  their  intuition, 
adding  an  element  of  certainty  by  the  discovery  of  the  animate 
agent. 

In  our  definition  of  infectious  diseases  we  must,  therefore,  empha- 
size the  animate  nature  of  the  pathogenic  agent.  We  will  state  that 
infectious  diseases  belong  to  the  class  of  parasitic  diseases ;  but  they 
here  occupy  a  special  place.    How  can  we  distinguish  them? 

Despite  our  endeavors,  the  distinction  will  necessarily  be  an  arti- 
ficial one.  All  attempts  at  classification  are  arbitrary,  since  distinc- 
tions rest  only  upon  differences  of  degree.  However,  let  us  attempt 
to  point  out  the  limits  between  the  two  groups. 

The  fundamental  character  of  the  parasite  is  to  live  at  the  expense 
of  the  being  it  inhabits  without  endangering  the  existence  of  its  host.- 
It  exerts  as  little  harmful  influence  upon  the  host  as  possible.  If  it 
ever  causes  death  it  is  as  a  matter  of  accident.  Parasites,  such  as 
intestinal  worms  and  cutaneous  parasites,  do  exert  a  toxic  action, 
but  this  is  of  a  local  character.  The  blue  spots  caused  by  the  pedic- 
ulis  pubis  express  an  intoxication  which  does  not  extend  beyond 
the  integument.  The  pustules  of  scabies  are  produced  by  secondary 
infections  facilitated  by  the  presence  of  the  specific  agent.  At  all 
events,  general  reactions  are  absent,  and  if  any  do  occur,  they  are  of 
a  reflex  nature,  such  as  might  be  occasioned  by  any  foreign  body, 
even  of  inorganic  nature,  that  irritates  the  nerve  terminations.    Even 


GENERAL  CONSIDERATIONS.  23 

hydatid  cyst  is  capable  of  exerting  only  mechanical  action.  If,  al  a 
given  moment,  It  gives  rise  to  serious  symptoms,  \\  is  -imply  by 
virtue  of  its  excessive  development,  under  which  circumstance 

compresses  Hie  adjacent  organs.    Ai.  any  rate,  it  does  not  .-i'-1  other- 
wise than  would  any  oilier  foreign  body  of  the  same  -i/-1. 
It  is  to  be  noted,  however,  that  all  parasites  contain  and  produce 

toxic  substances.  It  is  a  general  law  of  biology  that  vital  manifes- 
tations result  in  the  formation  and  excretion  of  noxious  products. 
On  the  other  hand,  a  foreign  body,  whether  of  organic  or  inorganic 
nature,  provokes  no  reaction,  either  local  or  general,  except  through 
the  agency  of  the  soluble  substances  which  it  diffuses.  An  abso- 
lutely insoluble  body  excites  no  reaction  whatever.  While  the 
amount  of  dissolved  matter  is  sufficient  to  influence  the  living  cells 
and  particularly  the  nerve  endings,  it  is  at  times  too  small  to  be 
detected  by  our  chemical  reagents.  Raulin's  and  Naegeli's  experi- 
ments in  this  connection  are  altogether  conclusive.  These  reflection- 
show  the  insignificant  value  of  our  classifications  and  demonstrate 
that  the  various  pathological  processes  are  related  to  each  other  by 
insensible  transitions. 

It  may  further  be  objected  that  certain  living  beings  may.  under 
certain  conditions,  be  considered  parasites  or  infectious  agents.  Such, 
for  instance,  is  the  case  with  oidium  albicans,  which  is  a  simple 
epiphyte  in  man  and  an  infectious  agent  in  animals.  I  think  these 
fungi  should  be  classed  with  the  infectious  agents  and  not  with  the 
true  parasites,  for  they  are  capable  of  causing  in  animals  a  mycosis 
analogous  to  bacterial  diseases.  Moreover,  their  subcutaneous  inocu- 
lation often  gives  rise  to  grave  general  manifestations,  and  may  pro- 
duce death  in  a  few  days.  In  man  such  an  evolution  is  rare,  but 
we  also  find  similar  facts  among  bacteria.  The  pneumococcal  strep- 
tococcus, staphylococcus,  and  colon  bacillus  live  upon  our  mucous 
membranes  as  inoffensive  parasites.  They  sometimes  provoke  small 
superficial  lesions  of  no  greater  importance  than  a  patch  of  aphtha. 
On  other  occasions  the}''  rise  to  the  rank  of  infectious  agents  and 
cause  violent  reactions. 

These  few  examples  show  how  numerous  are  the  transitions  be- 
tween infectious  and  parasitic  diseases.  Nevertheless.  I  believe  it  is 
possible  to  distinguish  the  two  groups  of  animate  agents  in  the 
following  manner : 

Parasitic  agents  exert  a  simple  mechanical  action  upon  the  econ- 
omy.   The  toxic  substances  produced  by  them  are  not  sufficiently 


24  INFECTIO  US  DISEASES. 

powerful  to  appreciably  impress  the  whole  organism.  They  give  rise 
only  to  some  local  phenomena. 

The  action  of  infectious  agents  upon  the  organism  is  complex. 
Their  mechanical  role  is  very  little,  if  at  all,  marked.  They  act 
mainly  through  the  noxious  substances  elaborated  by  them.  For 
this  reason  it  is  possible  to  say  that  infection,  in  the  last  analysis, 
is  intoxication  of  parasitic  origin. 

It  will  now  be  easier  for  us  to  understand  how  the  group  of  infec- 
tions should  be  formed.  Inspired  with  the  definition  proposed  by 
Prof.  Bouchard  for  disease  in  general,  we  shall  say:  Infectious  diseases 
are  characterised  by  the  phenomena  manifested  in  an  individual 
wlien  undergoing  the  action  of  parasitic  toxins  and  reacting  against 
them. 

Objections  could  be  raised  against  this  definition.  It  seems  to  the 
writer,  however,  that  it  is  quite  in  harmony  with  facts  actually 
known.  It  has  the  advantage  of  placing  clinical  phenomena  in  the 
first  rank,  and  at  the  same  time  it  takes  cognizance  of  etiology  and 
pathogenesis.  If  it  is  applicable  to  certain  parasitic  diseases,  it  is  so 
for  the  reason  that  facts  constitute  an  uninterrupted  chain  in  nature. 

Classification  of  Infectious  Diseases. 

An  exclusively  microbiological  classification  is  impossible,  since 
apparently  identical  clinical  manifestations  may  be  caused  by  differ- 
ent microbes,  and,  on  the  other  hand,  one  and  the  same  microbe  may 
give  rise  to  quite  different  manifestations. 

These  facts  are  well  known.  Suppuration,  for  instance,  may  be 
engendered  by  the  most  diverse  bacteria.  Likewise,  in  intoxications, 
many  poisons  produce  the  same  symptoms:  convulsions,  paralyses, 
coma.  To  recall  a  simpler  illustration,  excitation  of  a  nerve,  what- 
ever the  irritant  employed,  whether  physical,  chemical,  or  physio- 
logical, always  produces  the  same  effect.  The  organism  has  at  its 
disposition  but  a  limited  number  of  responsive  modes;  hence  it  is 
conceivable  that,  in  pathology  as  well  as  in  physiology,  different 
excitations  may  be  followed  by  similar  reactions. 

To  return  to  the  microbes.  Bacteriological  researches  have  demon- 
strated that  ulcerative  endocarditis  may  be  the  result  of  the  action 
of  the  most  varied  microbes.  The  same  is  true  in  regard  to  broncho- 
pneumonias, and  the  anatomicoclinical  distinctions  which  some 
authors  have  attempted  to  establish  according  to  the  nature  of  the 


( ; /<; A' E RAL  CONSIDERATIO ss.  2 6 

pathogenic  agent  have  been  proved  untenable  by  further  researches 
On  the  other  hand,  the  same  microbe  is  capable  of  exciting  markedly 
dissimilar  manifestations.  The  streptococcus,  for  instance,  produces 
phlegmon,  erysipelas,  septicemias,  pyemias,  bronchopneumonias, 
ulcerative  endocarditis,  etc.  The  same  is  true  of  the  staphylococcus, 
pneumococcus,  and  colon  bacillus,  which  are  mel  with  in  a  great 
variety  of  lesions. 

In  view  of  these  facts,  some  authors  attempted  to  attack  the 
modern  theories  of  pathogenesis  and  to  minimize  the  importance 
attributed  to  microbic  agents.  It  must  be  acknowledged  thai  at 
first  the  results  seemed  somewhat  deceiving;  but  a  comparative 
study  of  the  events  occurring  in  infections  and  in  intoxications  will 
show  that  the  same  dilliculty  exists  in  both. 

Any  given  poison  may  exert  wholly  different  effects.  Alcohol,  for 
instance,  may  cause  drunkenness,  delirium  tremens,  pachymenin- 
gitis, pseudotabes,  hepatic  cirrhosis,  etc.  The  same  is  true  of  other 
poisons,  such  as  phosphorus,  arsenic,  lead,  and  mercury.  On  the  other 
hand,  apparently  identical  phenomena  may  be  due  to  the  action  of 
different  poisons  or  occur  even  without  the  agency  of  any  intoxication. 

The  results  are,  therefore,  comparable  in  the  various  morbid  groups, 
and  their  study  clearly  demonstrates  the  impossibility  of  purely 
etiological  classifications.  The  inconstancy  of  results  does  not,  how- 
ever, constitute  an  exception  to  determinism,  which  is  the  basis  of 
all  science.  If  the  manifestations  are  dissimilar  while  the  cause  i- 
the  same,  this  is  due  simply  to  the  fact  that  the  action  of  the  c 
is  exercised  under  different  conditions.  We  must  remember  that  no 
two  individuals  are  alike.  Heredity  and  innateness  impose  upon  each 
person  a  particularism  which  becomes  more  marked  as  years  pass 
and  the  organism  is  subjected  to  numerous  external  influences.  Since 
individuals  are  different,  reactions  cannot  be  identical.  The  facts 
observed  by  the  physician  are  not,  therefore,  results  of  accident,  but 
thejr  are  so  complicated  and  so  varied  that  it  is  impossible  to  unite 
them  in  a  simple  formula. 

These  reservations  should  not  prevent  the  nosologist  from  taking 
cognizance  of  etiological  data  which,  though  always  interesting,  have 
acquired  additional  importance  since  the  discovery  of  specific  serums. 
Bacteriological  subdivisions  should,  therefore,  be  introduced  into 
clinical  groupings. 

Specific  and  Non-specific  Infections.  In  the  first  place,  infections 
may  be  divided  into  two  large  classes,  specific  and  non-specific. 


26  INFECTIOUS  DISEASES. 

Iii  specific  infections  the  pathogenic  agent  suffices  to  characterize 
the  disease.  Such,  for  instance,  are  anthrax,  tuberculosis,  and  diph- 
theria. This  class  is  divisible  into  three  orders  according  as  the 
pathogenic  parasite  is  a  bacterium,  a  more  highly  organized  plant, 
or  an  animal  agent.  A  fourth  order,  which  will  sooner  or  later  dis- 
appear, comprises  those  infections,  such  as  hydrophobia,  syphilis, 
typhus  fever,  and  scarlatina,  the  pathogenic  agents  of  which  have 
not  yet  been  discovered. 

Non-specific  infections  differ  from  the  preceding  by  the  following 
characters :  1 .  They  are  due  to  common  bacteria  almost  constantly 
inhabiting  our  mucous  membranes  and  skin,  vegetating  as  simple 
saprophytes.  2.  Each  clinical  type  may  be  produced  by  different 
agents.  3.  Each  microbe  may  give  rise  to  the  most  varied  manifes- 
tations. 

Non-specific  infections  comprise  exudative  inflammations,  such  as 
erysipelas;  suppurative  processes,  such  as  phlegmon;  degenerative 
conditions,  such  as  grave  icterus ;  pseudomembranous  inflammations, 
such  as  certain  non-diphtheritic  sore  throats;  ulcerating  affections, 
such  as  infectious  endocarditis,  and  necrosing  processes,  such  as  pul- 
monary gangrene.  Now,  the  feature  of  dominant  importance  in  the 
history  of  these  diseases  is  not  the  nature  of  the  pathogenic  agent, 
but  the  morbid  localization.  The  same  microbe,  staphylococcus 
aureus,  for  example,  produces  furuncle,  osteomyelitis,  and  ulcerative 
endocarditis,  yet  no  one  would  think  of  including  in  one  chapter 
affections  so  different  from  each  other.  These  non-specific  infections 
must,  therefore,  be  considered  in  connection  with  the  organs  in  which 
the  process  is  localized,  and  with  other  ulcerations  which  may  affect 
the  same  viscera. 

Subdivisions  of  Specific  Infections.  We  will  admit  two  groups  in  the 
class  of  specific  infections,  placing  general  infections  of  septicemic 
or  pyemic  character  in  the  first  group,  and  in  the  second  those  in 
which  visceral  localization  immediately  attracts  the  clinician's  atten- 
tion as  a  matter  of  prime  importance. 

The  general  specific  infections  comprise  three  classes:  eruptive 
infections,  septicemic  infections,  and  infections  with  nodular  pro- 
ductions. 

Eruptive  injections  possess  an  indisputable  autonomy.  They 
cannot  be  ranked  among  infections  with  cutaneous  determination. 
They  are  general  diseases,  veritable  septicemias,  ushered  in  with 
symptoms  expressing  an  impregnation  of  the  whole  organism.    Sub- 


GENERAL  CONSIDERATIONS.  il 

sequently  a  sort  of  discharge  toward  the  mucous  membrane*  and  Hi'- 
skin  takes  place,  relieving  the  principal  symptoms.  The  discharge 
may  be  characterized  by  erythema,  as  in  measl 
rubeola,  and  sudor  anglicusj  by  vesicles,  as  in  zona;  by  bulls,  ac 
in  varicella  and  polymorphous  erythema;  by  vesicopustuies,  ae  in 
vaccinia  and  smallpox.  I  lere  belongs  syphilis.  "Venereal  dia 
is  a  denomination  which  should  become!  obsolete  or  be  preserved  only 
for  convenience.  Otherwise,  it-  is  wrong  to  form  a  group  of  di  i 
which  have  no  relationship  to  each  other  excepl  the  fact  that  in  the 
majority  of  cases  they  are  contracted  through  sexual  intercourse, 
though  this  etiological  circumstance  is  not  indispensable.  Syphilis 
begins  as  a  local  lesion,  followed  by  a  general  impregnation  of  the 
economy.  Later  on  a  discharge  takes  place  toward  the  integuments. 
This  evolution,  although  slower,  is  identical  with  that  of  smallpox. 
The  comparison  is  altogether  perfect  if  we  select  inoculated  smallpox : 
in  this  case  there  is  a  local  lesion  followed  by  general  impregnation 
and  secondary  eruption.  The  only  difference  resides  in  the  fact 
that  syphilis  runs  a  much  slower  course  and,  therefore,  the  reactions 
are  less  intense.  It  is  well,  however,  to  remark  that  the  comparison 
is  exact  only  during  the  first  periods  of  the  disease.  After  a  certain 
lapse  of  time  syphilis  gives  rise  to  lesions  which  render  it  quite  unlike 
eruptive  fevers.  At  this  stage,  however,  the  virus  is  profoundly 
modified.  Its  contagiousness  is  nil  or  so  slight  that  contamination 
by  tertiary  accidents  was  long  denied,  and  very  few  cases  are  quoted 
even  at  the  present  day.  This  leads  to  the  belief  that  syphilis  is  due 
to  a  parasite  which  undergoes  a  long  course  of  evolution  within  the 
infected  organism.  After  having  provoked  a  highly  contagious 
exanthematic  septicemia,  it  becomes  localized  at  certain  points  and 
produces  local  and  non-transmissible  lesions  of  a  quite  different 
nature. 

The  second  group  comprises  the  infection*  with  septicemic  tendency 
exclusive  of  eruptive  fevers.  The  author  classes  in  this  group  typhoid 
fever,  typhus,  influenza,  bubonic  plague,  and  anthrax.  Typhoid 
fever  might  be  placed  among  infections  of  an  intestinal  determina- 
tion, but  the  digestive  disturbances,  important  as  they  are,  do  not 
represent  the  principal  symptom  of  the  malady.  The  general  reac- 
tions expressing  the  impregnation  of  the  whole  organism  are  oi 
greater  importance.  The  same  remark  is  applicable  to  bubonic 
plague,  the  danger  from  which  likewise  results  from  the  invasion  of 
the  organism  by  the  specific  bacillus.    The  same  is  true  of  anthrax: 


28  IXFECTIO  US  DISEASES. 

it  is  not  the  local  lesion  that  kills;  on  the  contrary,  the  prognosis 
depends  upon  the  resistance  of  the  organism  to  general  infection. 

The  infections  with  nodular  productions  seem  to  me  to  constitute 
a  group  so  natural  as  to  require  no  further  discussion.  Glanders  links 
this  group  with  septicopyemic  infections.  Tuberculosis,  leprosy, 
and  nodular  mycoses  are  characterized  by  entirely  comparable  reac- 
tionary manifestations. 

Non-specific  infections  are  classified  according  to  the  predominat- 
ing symptoms.  In  the  majority  of  cases  these  symptoms  are  ex- 
plained by  the  localization  of  the  parasite.  Tetanus  alone  is  to  be 
excepted.  The  author  has  placed  this  disease  among  the  infections 
with  nervous  localization.  Of  course,  the  pathogenic  agent  remains 
localized  at  some  point  of  the  economy,  most  frequently  in  the 
cellular  tissue,  at  times  in  some  organ,  and  does  not  reach  the  nerve 
centres  at  all,  thus  behaving  otherwise  than  the  parasite  of  hydro- 
phobia. The  nervous  manifestations  are,  however,  so  predominant 
that  the  clinician  hesitates  to  assign  to  tetanus  some  other  position 
in  nosology.  At  all  events,  the  author's  view  is  in  accordance  with 
his  definition  of  infectious  diseases,  since  their  characteristics  must 
be  sought  in  the  reaction  of  the  organism  to  the  action  of  microbic 
toxin.     The  localization  of  the  latter  should  guide  the  nosologist. 

The  writer  has  advisedly  closely  allied  recurrent  fever  and  palu- 
dism.  These  two  diseases  seem  to  form  a  very  natural  group  in  the 
classification.  Their  agents  localize  themselves  in  the  organs  con- 
nected with  the  blood  system,  notably  in  the  spleen,  and,  at  a  certain 
moment,  invade  the  blood  itself. 

As  to  the  other  infections,  classification  was  easier.  It  was  quite 
natural  to  place  dysentery  and  cholera  among  infections  with  intes- 
tinal determination;  yellow  fever  among  infections  with  hepatic 
determination,  etc. 

The  author's  classification  is,  of  course,  subject  to  modification. 
He  has,  however,  taken  into  account  the  chief  characters  of  infections 
without  neglecting  the  etiological  data.  He  subdivides  all  infections, 
according  to  the  causative  agent,  into  infections  of  bacterial,  mycosic, 
or  animal  origin.  In  a  last  group  are  placed  those  diseases  in  which 
the  causative  agents  are  as  yet  unknown. 


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This  classification  is  naturally  of  a  provisional  character.  Tuber- 
culosis, for  instance,  has  been  placed  in  its  customary  position — viz., 
among  bacterial  infections.  It  should,  however,  be  classed  with 
mycosic  infections  if  its  agent  is  an  oospora.  In  view  of  the  contri- 
butions of  Lesage,  Achalme,  Triboulet,  Coyon,  Laveran,  and  Catrin, 
the  author  has,  with  reserve,  classed  measles,  acute  articular  rheu- 
matism, and  mumps  as  bacterial  infections.  Supported  by  researches 
which  the  writer  is  pursuing  with  Dr.  Weil,  and  by  the  more  recent 
work  of  Funck,  smallpox,  varicella,  and  vaccinia  have  been  placed 
among  the  diseases  due  to  animal  microbes.  Finally,  dysentery  has 
been  divided  into  two  distinct  affections  which  are  akin  sympto- 
matically,  but  different  as  to  their  pathogenic  agents. 

Tumors  and  lymphadenia  are  excluded,  although  their  parasitic 
nature  seems  highly  probable. 

In  this  tentative  classification  of  infectious  diseases  the  actual 
process  alone  is  taken  into  account,  viz.,  that  which  is  connected 
with  the  life  of  the  pathogenic  agent.  When  the  latter  is  destroyed 
the  morbid  evolution  does  not  stop.  Here  is  brought  to  light  an 
interesting  difference  between  parasitic  and  infectious  diseases:  in 
the  former  all  symptoms  vanish  with  the  parasite;  in  the  latter 
certain  disturbances  persist  and  run  an  independent  course  of  evo- 
lution. Organic  affections,  which  are  often  developed  in  a  slow, 
insidious  manner,  are  thus  created,  and  in  some  accidental  way  a 
cardiac  lesion,  for  instance,  connected  with  a  typhoid  fever  suffered 
in  childhood,  and  which  has  taken  fifteen  or  twenty  years  to  develop, 
is  discovered  in  the  adult.  This,  however,  is  of  little  practical  im- 
portance, since  the  organic  lesion  is  wholly  independent  of  the  causa- 
tive affection  of  long  ago.  The  sequelae  of  infections  are,  therefore, 
rightly  described  as  affections  of  the  organs  bearing  no  stamp  of  their 
origin. 

History  of  Infectious  Diseases. 

It  has  always  been  admitted  that  infectious  diseases  may  be  trans- 
mitted by  the  air  and  by  contact  with  the  sick.  Hippocrates  speaks 
solely  of  the  former  mode,  as  do  also  the  writers  and  poets.  As  late 
as  the  sixteenth  century  no  important  document  concerning  the  con- 
tagiousness of  disease  is  furnished  us  by  medical  literature.  The 
ancients  were  not,  however,  ignorant  of  the  transmission  of  disease 
by  contact.  It  was  evidently  for  fear  of  contagion  that  Moses  ordered 
the  isolation  of  persons  afflicted  with  leprosy  or  gonorrhea.     It  was 


GENERA  L  OONSIDERA  'floss.  :>) 

the  same  etiological  notion  that,  al  the  end  of  the  fourteenth  cen 
tury,  caused  in  Italy  the  isolation  of  persons  who  had  conic  in  contacl 
with  plague-stricken  individuals. 

Disregarding  the  useless  controversy  which  raged  about  the  que* 
tion  of  the  contagiousness  of  diseases,  lei  us  briefly  review  the  idea* 
which  successively  prevailed  as  to  the  nature  of  the  principle*  thai 
served  for  their  transmission. 

Two  great  theories  have  always  been  advocated.  One,  the  chemi- 
cal, assumes  the  cause  of  diseases  to  be  a  volatile  or  fixed  principle 
emanating  from  the  soil,  bodies  of  animals,  or  men.  The  other,  a 
vital  one,  asserts  the  action  of  infinitely  small  living  beings  which 
penetrate  and  develop  within  the  organisms  of  men  or  animal-. 

Some  of  the  advocates  of  the  chemical  doctrine  thought  the  mor- 
bific principles  were  volatile.  This  conception  was  so  deeply  rooted 
that  Henry  VIII.  caused  his  Minister  (Wolsey)  to  be  tried  for  having 
spoken  into  his  majesty's  ear;  he  accused  him  of  an  attempt  to 
transmit  syphilis  to  him  through  the  agency  of  his  breath.  Syden- 
ham and  Cullen  believed  that  contagion  was  effected  by  vapors  rising 
from  the  human  body.  However,  the  practice  of  variolization  and 
vaccination  clearly  demonstrated  that  the  viruses  were  not  always 
volatile.  The  profession  was  thus  led,  at  the  beginning  of  the  nine- 
teenth century,  to  admit  two  orders  of  contagion :  one  volatile,  that 
is,  the  air  charged  with  putrid  vapors;  the  other  fixed,  multiplying 
within  the  organism. 

What,  however,  is  the  nature  of  this  fixed  virus?  Fracastor  had 
already  compared  the  development  of  disease  to  putrefaction,  with- 
out, of  course,  suspecting  the  animate  origin  of  the  latter  process. 
He  thought  that  germs  developed  and  served  for  the  propagation 
of  the  malady.  The  same  idea  was  taken  up  by  Henle  (1840),  who 
believed  that  contagious  diseases  were  due  to  organic  particles  eman- 
ating from  the  living  organism  and  preserving  their  pathogenic 
power.  Ch.  Robin's  theory  hardly  differed  from  the  preceding  one : 
"Virulent  diseases  are  those  in  which  the  fundamental  organic  sub- 
stance or  substances  of  one  or  of  all  the  humors  have  undergone  a 
specific  modification,  which  modification  is  transmitted  to  organic 
substances  themselves  and  then  to  the  organized  substance  of  an- 
other living  being.  ...  As  to  the  creation  of  the  virulent  state, 
it  is  the  same  phenomenon  as  the  one  that  occurs  for  the  formation 
of  the  organic  substances  themselves  by  isomeric  catalysis.1"     That 

1   l.ittre  et   Robin.     Diet,  de  mod.,  art.  Inoeulable  et  Virulent.  Pari-.  1878,  14th  ed. 


32  I HTFE(  'TIOl  's  DISEASES. 

norma]  substances  should  undergo  analogous  alterations  on  coming 
in  contact  with  some  modified  organic  matter  was  not  far  from  con- 
ceivable;  but  the  doctrine  fails  to  explain  the  appearance  of  the 
modified  state.  It  does  not  offer  an  acceptable  theory  by  comparing 
the  development  of  virulent  diseases  to  the  formation  of  organic 
substances.  This  brought  into  the  domain  of  pathogenesis  the  cur- 
rent ideas  upon  spontaneous  generation.  Even  the  great  discovery 
<>f  Villemin  did  not  suffice  to  overthrow  the  erroneous  theories,  as 
it  only  established  the  transmissibility  of  tuberculosis  from  sick  to 
healthy  individuals.  Although  of  great  importance  from  the  stand- 
point of  hygiene  and  prophylaxis,  it  did  not  reveal  the  nature  of  the 
pathogenic  agent. 

Even  previous  to  this  epoch,  however,  certain  minds  were  im- 
pressed by  the  analogies  existing  between  the  development  of  infec- 
tious diseases  and  that  of  animals  and  plants.  It  was  merely  a  com- 
1  larison,  but  was  destined  to  be  a  highly  fertile  one.  Solid  arguments, 
however,  did  not  appear  until  the  beginning  of  the  nineteenth  cen- 
tury. By  a  sort  of  divination,  some  minds  began  to  perceive  the 
truth.  Hildebrand,  in  his  book  on  contagious  typhus  (1811),  showed 
that  miasms  spread  and  multiplied  like  the  germs  of  living  beings. 
About  the  same  period  J.  Hamean,  a  country  physician,  to  whom 
is  due  one  of  the  first  observations  of  the  transmissibility  of  glanders 
from  the  horse  to  man,  argued  that  virulent  matters  possessed  a  life 
principle,  since  they  acted  like  parasitic  insects.  He  further  stated 
that  there  is  an  antagonism  between  certain  viruses,  such  as  variola 
and  vaccinia,  and  transitory  viruses,  such  as  scarlatina,  and  the 
bodies  which  they  leave,  since  they  attack  them  no  more — i.  e.,  confer 
immunity.  It  must  be  admitted,  therefore,  that  viruses  produce 
within  the  body  excrementitious  substances  which,  so  long  as  they 
are  not  eliminated,  inhibit  their  action.  Hamean  thus  perceived  the 
mechanism  of  acquired  immunity  as  it  is  admitted  at  present.1  Budcl 
asserted  (1850)  that  cholera  was  transmitted  by  germs,  and,  in  1870, 
he  assumed  that  living  organisms  represented  the  specific  cause  of 
contagious  diseases.  Bouillard  accepted  the  same  idea,  and  Trous- 
seau, in  a  famous  lecture,  showed  that  infectious  diseases  were  trans- 
mitted by  living  germs:  "The  facts  of  contagion,"  said  he,  "would 
thus  materially  be  explained,  if  the  presence  of  these  spores  in  the 
atmosphere  could  be  discovered.    To  attain  this  result  one  should 

1  J.  Hamean.     Etudes  sur   les  virus  (1836-1847).     Edition   preceded   by  a   preface 
by  Prof.  Grancher,  Paris,  1895. 


QENERA  l<  CONSIDERATIONS.  33 

follow  the  path  traced  by  M.  Pasteur  and  proceed  with  the 
experimental  ability  and  patience."1    II.  Gueneau  de  Mussy  (1878), 
in  his  preface  to  the  translation  of  Murchison's  booh  on  typhoid 
fever,  pleads  in  favor  of  the  parasitic  doctrine  and  points  oui  the 
respective  parts  played  by  the  seed  and  the  soil. 

However,  these  pathogenic  conceptions,  which  were  arrived  at  by 
reasoning,  were  to  be  followed  and  confirmed  by  bacteriological 
researches.  The  first  step  was  to  attribute  infections  to  relatively 
highly  organized  parasites.  Van-on  and  Columelle  speak  of  diseases 
engendered  by  insects  spread  in  the  air.  In  the  sixteenth  and  seven- 
teenth centuries  analogous  ideas  were  developed  by  various  obser- 
vers. Infusoria  were  described  by  Languis  for  measles;  by  Zacutue 
for  smallpox;  by  Kircher  for  the  plague.  On  the  other  hand,  Lancisi, 
Reaumur,  and  Linne  supported  with  their  great  authority  the  ani- 
mate nature  of  contagions.  Deidier  admitted  the  agents  of  syphilis 
to  be  worms;  Goiffon  (of  Lyons),  in  1721,  believed  that  invisible 
insects  transported  the  plague.  This  coarse  parasitism  reached  its 
height  with  Raspail. 

The  true  pathogenic  agents  had,  however,  been  seen  as  earl}-  afi 
1850.  In  that  year  Rayer  communicated  to  the  Societe  de  Biologie 
observations  which  he  had  made  with  Davaine  upon  the  blood  of 
sheep  infected  with  anthrax.  By  examining  under  the  microscope 
a  drop  of  blood  derived  from  the  dead  animal, they  had  seen  "minute 
filiform  bodies  about  twice  as  long  as  the  diameter  of  a  red  blood 
corpuscle.  These  little  bodies  presented  no  spontaneous  move- 
ments." Pollender  and  Brauell  rediscovered  these  same  elements. 
Delafond,  in  1860,  considered  them  as  plants  and  attempted  to  cul- 
tivate them,  and  even  endeavored  to  demonstrate  the  spores.  He 
failed  at  the  latter  point.  The  existence  of  anthrax  spores  was  to 
be  demonstrated  sixteen  years  later  by  Robert  Koch. 

In  spite  of  the  important  discoveries  which  enriched  the  history 
of  anthrax,  no  one  had  understood  the  pathogenic  role  of  the  rods, 
to  which  a  prognostic  value  alone  was  attributed.  The  true  concep- 
tion was  gradually  attained  in  an  indirect  manner  by  the  study  of 
fermentations.  Rhazes,  Hoffmann,  Bressy,  and  others  compared 
infections  to  fermentations,  a  comparison  of  great  interest.  Unfor- 
tunately, however,  the  cause  of  fermentations  was  just  as  little 
understood  as  was  that  of  infections. 

1  Trousseau.     De  la  contagion.     Clinique  med.  de  l'Hotel  Dieu.  t.  i    p.  593-622. 

3 


34  l.MECTIOUS  DISEASES. 

The  fact  is  that  an  erroneous  doctrine,  prevailing  since  the  time 
of  Aristotle,  prevented  advance  along  this  line.  Reference  is  here 
made  to  the  idea  of  spontaneous  generation.  Redi,  in  1668,  was 
the  first  to  rise  against  this  dogma.  Transporting  the  problem 
to  experimental  ground,  he  showed  that  the  larva1  of  flies  were 
not  born  spontaneously  through  putrefaction  of  meat.  When  the 
insects  were  prevented  from  depositing  their  eggs  no  larvse  could 
develop. 

Soon  after,  in  1678,  van  Leeuwenhoek  discovered  in  infusions 
minute  animals  which  Wrisberg,  in  order  to  indicate  their  origin, 
named  infusoria.  Van  Leeuwenhoek  admitted  that  these  minute 
beings  floated  in  the  atmosphere,  but  his  view  was  not  acceptable 
to  all.  and  his  researches  became  the  subject  of  memorable  contro- 
versies, principally  between  Needham  and  Spallanzani.  The  latter 
proved  by  admirable  experiments  that  infusions  remained  sterile 
when  well  protected  from  the  germs  of  the  atmosphere.1  This  dis- 
covery was  confirmed  and  completed  by  Schulze  and  Schwann  at  the 
beginning  of  the  nineteenth  century.  Finally,  in  1837,  Cagnard- 
Latour  demonstrated  the  numerical  and  ponderable  increase  of  yeast 
in  the  course  of  the  fermentative  process  and  established  its  animate 
nature.  Still,  Liebig's  school  persisted  in  attributing  fermentation 
to  the  action  of  some  decaying  substance. 

Such  was  the  state  of  the  question  wThen  Pasteur's  researches  on 
the  lactic  acid  ferment  (1857),  the  alcoholic  ferment  (1860),  and 
finally,  on  some  anaerobic,  viz.,  butyric  ferment  (1861),  were  suc- 
cessively published. 

Pasteur's  researches  on  silkworm  diseases  (1865-1870)  may  be 
considered  as  the  fundamental  work  from  which  the  era  of  the  new 
discoveries  and  doctrines  dates.  Unfortunately,  these  researches 
were  ignored  or  uncomprehended  by  the  medical  world.  Davaine, 
however,  had  surmised  that  disease  as  well  as  fermentation  depended 
upon  animate  agents,  and  accumulated  a  considerable  amount  of 
experimental  facts  in  support  of  this  conception.2  In  spite,  however, 
of  the  admirable  investigations  of  Davaine,  and  the  discovery  of 

1  Spallanzani.  Observations  et  exp.  faites  sur  les  animalcules  des  infusions. 
CEuvres  completes  (Trad.  Senebier),  1787,  t.  i.  Observations  et  exp.  sur  l'origine  des 
petites  plantes  des  moisissures.     Ibid.,  t.  ii.  p.  286-309. 

2  Davaine.  Recherches  sur  les  infusoires  du  sang  dans  la  maladie  connue  sous  le 
nom  de  sang  de  rate.  Comptes  rendus,  1863.  Davaine  published  a  great  number  of 
notes  inserted  into  the  C.  R.  of  the  Academy  of  Science,  Academy  of  Medicine,  and 
Society  of  Biology.     They  are  collected  in  l'GEuvre  de  Davaine,  Paris,  1889,  t.  i. 


GENERA  L  CONSIDERS  TI0N8.  ;;.". 

anthrax  spores  by  Koch,'  the  p;ir;isitic  theory  of  infectiou  di 
had  few  adherents.  Further  opposition  was  rendered  impoi  >\' 
however,  when  Pasteur,2  by  the  method  of  culture  .  demon  trated 
beyond  all  doubt  that  anthrax  is  caused  by  the  bacillus  anthracie 
as  scabies  is  caused  by  the  acarus  scabiei.  A  few  years  Inter  bacte- 
riological  doctrines  received  official  sanction  a1  the  Paris  Faculty  of 
Medicine  by  Prof.  Bouchard,  who  was  the  first  to  study  the  role 
played  by  animate  agents  in  the  genesis  of  infections. 

This  was  in  1880  and  [881,  when  reaction  was  intense.  Opposition 
gradually  gave  way  to  successive  discoveries  which  established  be- 
yond dispute  that  infections  are  due  to  parasites  some  vegetable, 
others  animal,  most  of  them  of  a  bacterial  nature. 

Classification  of  Infectious  Agents. 

Pathogenic  Bacteria.      For  reasons  already  referred  to  we  cannot, 
as  do  some  authors,  regard  "infectious"  and  "bacterial"  diseas 
synonymous.    Admitting,  however,  the  considerable  pathogenic  role 
of  bacteria,  we  shall  begin  the  history  of  pathogenic  agents  by  a  study 
of  them. 

At  present  bacteria3  are  generally  considered  as  belonging  to  the 
family  of  algae,  and  not,  as  was  formerly  believed,  to  that  of  the  fungi. 
Hence,  the  name  schizophycetes4  would  be  more  suitable  than  schizo- 
mycetes,5  generally  employed  since  Naegeli's  time. 

From  a  purely  medical  standpoint,  bacteria  are  divided  into  two 
groups  under  the  names  saprophytic  and  pathogenic,  according  as 
they  develop  in  dead  or  in  living  organisms.  Though  highly  im- 
portant, this  division  is  not  complete.  We  think  it  is  well  to  add  a 
third  group — that  of  parasitic  bacteria — which  vegetate  upon  living 
organisms  without  inflicting  any  appreciable  harm.    It  is  also  to  be 

1  R.  Koch.  Die  Aetiologie  der  Milzbrand-krankheit.  Cohn's  Beitr.  zur  Biol,  der 
Pflanzen,  1S76. 

2  Pasteur,  Joubert,  Chamberland  et  Roux.  Numerous  notes  published  in  the 
Comp.  Rend,  of  the  Academy  of  Science,  beginning  with  1877. 

3  Bacterium  (from  .lanrtipiov,  a  little  stick,  diminutive  of  Sanri/pia,  a  stick,  staff. 
plural,  bacteria)  is  a  general  name  applied  to  microbes  entering  the  group  of  schizo- 
phytes.  The  term  bacterium  should  not  be  employed  as  synonymous  with  microbe. 
The  latter  (JSlinpoc,  small,  3ioc,  life")  is  used  to  designate  all  microscopic  beings  of  vege- 
table or  animal  nature. 

4  Schizophycetes  (oxKsiv,  cleave,  split:  error,  plant),  alga;  which  multiply  by 
division  or  fission. 

5  Schizomycetes  (ty^ftfetv,  to  cleave.  Mvtajr,  pi.  Mwra/rej-j  a  fungus),  fungi  which 
multiply  by  cleavage  or  fission;  hence  fission  fungi. 


36  I SFECTIOUS  DISEASES. 

remembered  that  the  same  bacterium  may  sometimes  be  a  sapro- 
phyte and  at  times  a  parasite,  and  on  other  occasions  rise  to  the  rank 
of  a  pathogenic  agent.  It  is  true  that  there  are  bacteria  which,  thus 
far,  have  always  seemed  to  be  devoid  of  virulence,  and  their  cultures 
injected  into  animals,  even  in  large  doses,  induce  no  disturbance. 
There  are,  however,  others  which  are  capable  of  passing  from  the 
state  of  a  saprophyte  to  that  of  a  pathogenic  agent;  and,  recipro- 
cally, the  majority  of  infectious  bacteria  may  have  a  saprophytic 
life.  It  is  not,  therefore,  indulging  in  pure  hypothesis  to  admit  that 
microbes  have  accidentally  become  morbific  and  that  it  is  by  accident 
that  they  pass  from  a  saprophytic  to  a  pathogenic  life. 

In  view  of  these  facts,  some  preferred  to  classify  microbes  according 
to  other  characters,  notably  their  biological  properties.  Pasteur,  who 
attached  little  importance  to  morphology,  considered  fermentative 
processes  of  far  greater  consequence.  He  believed  that  by  studying 
the  modifications  which  microbes  produced  in  well-defined  products 
it  was  possible  to  reach  a  sure  classification.  Fermentative  action, 
however,  has  no  fixed  characters.  Several  different  bacteria  may 
give  rise  to  the  same  products.  Moreover,  within  a  well-defined 
species  are  found  varieties  enjoying  similar  fermentative  powers. 
Finally,  by  means  of  successive  cultures  the  action  upon  media 
may  be  modified. 

There  is,  however,  an  action  which  is  considered  by  most  authors 
to  be  of  considerable  diagnostic  importance,  viz.,  the  peptonization 
of  gelatin.  Hence,  the  majority  of  bacteriologists  divide  microbes 
into  those  which  liquefy  gelatin  and  those  which  do  not.  This  char- 
acter is  evidently  of  real  interest,  but  there  is  no  reason  for  attrib- 
uting to  it  an  absolute  value  sufficient  to  separate  species  which, 
in  other  respects,  seem  to  be  closely  allied. 

A  natural  classification  of  bacteria  requires  cognizance  of  the 
greatest  possible  number  of  characters.  Such  an  attempt,  at  the 
present  stage  of  the  science,  is  premature.  It  is  better  to  be  guided 
by  some  objective  character  of  sufficient  constancy  and  appreciable 
without  much  difficulty.  Accordingly,  the  majority  of  authors  have 
taken  morphology  as  a  basis. 

Without  enlarging  upon  all  classifications  that  have  been  proposed, 
the  author  believes  that  bacteria  may  be  grouped  in  the  following 
simple  manner: 


Corel 


GENERA  l,  00N8IDEBA  'floss.  :>,, 


I  >iploco< 

I I  tracoi 

-  1  |.    p|  .,<•.,<■..! 

Stapi 

Mei  i  mop  difl . 

Leuconi 

\  ecu 


Bacilli(rod-shaped) 


I  mum 

Bacillu 
l  <epto1  in  i  •. 
I  • 

( Irenol  liri  x. 
Cladol  liri  \ . 


Vibrion. 
Curved  bacteria  j  Spirillum 


'  Bpirochast  •■> . 


Cocci  (x°XX°Z)  berry,  grain)  ;m>  round   elements,  almost  always 

non-motile  and  sporeless.  According  as  the  elements  arc  isolated  or 
agminated,  they  are  called  monococci,  diplococci,  and  tetracocci; 

when  in  the  form  of  a  chain,  streptococci,  and  when  presenting  the 
shape  of  grape  bunches,  staphylococci.  These  divisions  are  of  no 
great  importance,  since  the  same  species  may  appear  under  several 
aspects.  It  is  true,  however,  that  it  assumes  by  preference  one  of 
these  aspects  which  serves  as  its  characteristic  feature. 

The  merismopedise  are  constituted  by  cells  or  plates  arranged  on 
a  plane.  In  sarcina?  the  mode  of  division  is  peculiar.  It  has  three 
planes  of  division.  Leuconostoc  and  ascococci  are  of  little  importance 
from  a  medical  standpoint. 

The  group  of  rods  contains,  in  the  first  place,  the  bacteria  and 
bacilli.  The  former  are  short  and  often  ovoid  in  form;  the  latter  are 
cylindrical.  This  distinction,  however,  is  gradually  being  displaced, 
and  the  term  bacilli  is  now  almost  universally  employed. 

The  leptothrix  occurs  in  the  form  of  a  more  or  less  segmented 
filament.  The  crenothrix  presents  the  same  aspect,  except  that  it 
is  surrounded  by  an  envelope.  The  cladothrix  is  characterized  by 
the  presence  of  lateral  filaments,  so  that  some  authors  have  taken 
it  to  be  a  higher  organism  than  the  bacteria  and  confounded  it  with 
the  streptothrix.  In  an  important  contribution,  Sauvageau  and 
Radais  demonstrated  that  in  cladothrix  there  are  no  real  branchings. 
There  are  only  new  elements,  produced  by  fission,  which  remain 
attached  to  each  other.  They  constitute  a  colony,  not  an  individual. 
It  is  important  to  emphasize  this  point,  since  authors  often  confound 
the  two,  and  it  is  not  clear  whether  they  refer  to  cladothrix  or 
streptothrix. 


38  INFECTIOUS  DISEASES. 

The  third  and  last  group  is  composed  of  curved  elements.  Some 
have  the  shape  of  a  comma  or  of  an  S.  These  are  the  vibrios. 
Others  present  the  form  of  spirals.  When  the  screw-like  turns  are  few 
in  number  and  less  close,  the  elements  are  called  spirilla;  when  the 
contrary  is  the  case,  they  are  sometimes  designated  as  spirochete. 

It  is  often  a  matter  of  difficulty  to  clearly  indicate  the  respective 
value  of  characters  attributed  to  various  groups.  For  instance,  it 
is  generally  admitted  that  there  are  numerous  analogies  between  the 
colon  bacillus,  the  pneumobacillus,  and  the  typhoid  bacillus.  One 
might  add  even  the  bacillus  of  pseudotuberculosis  of  rodents.  Should 
these  various  types  be  considered  as  distinct,  though  allied,  species, 
or,  on  the  contrary,  do  they  represent  varieties  that  may  be  trans- 
formed into  each  other?  The  delicate  question  has  long  been  the 
subject  of  controversy.  Moreover,  the  colon  bacillus  and  pneumo- 
bacillus vary  extreme^  in  form,  biological  properties,  and  pathogenic 
potency.  We  are,  therefore,  led  to  presume  that  these  species  com- 
prise numerous  varieties  which  have  often  been  described  as  new 
species. 

Over  two  hundred  pathogenic  bacteria  are  actually  known.  They 
may,  in  this  respect,  be  divided  into  two  groups  according  as  they 
produce  a  well-defined  disease  or  give  rise  to  various  pathological 
processes.  Such  a  division  is  in  harmony  with  the  expressions 
"specific"  and  " non-specific."  Taking  morphology  into  account 
at  the  same  time,  we  reach  the  following  classification  in  which  the 
principal  species  alone  are  included: 

Xox-specific  Bacteria. 

Micrococci. 

/-aureus. 
Pyogenic  staphylococcus  .  .  <  citreus. 

lalbus. 
Streptococcus  .....  very  numerous  varieties. 

Pneumocoecus   (Streptococcus  pneumonia;)  . 
Tetragenus       ...... 

Bacilli. 


falbus. 
t  citreus. 


Colon  bacillus 


Pneumobacillus 


B.  lactis  aerogenes. 
B.  neapolitanus. 
B.  pyogenes  fcetidus. 
B.  enteritidis. 
B.  endocarditis  griseus. 
pyobacillus  Fischeri. 
B.  cavicida. 

septic  bacillus  of  the  bladder, 
pyogenic  bacterium, 
.paracolon  bacillus. 
B.  of  rhinoscleroma. 
B.  hominis  capsidatus. 
B.  capsulatus  septicus. 
B.  endocarditis  capsidatus. 


( ;  E A' EBAL  00 NS TDERATIO N8.  39 

r>.    of    f  > i  i  baoosis. 

I:,  of  bemorrh   sepl Lcemiae. 

li.  aepticua  putidus, 

■  /■/ .,/.  //    in  u  niiii i  . 
Proteus  vulgaris      ....  Proteu    pleomorphu  . 

i  /', ,,/, ,/    ,  /it ,i  a  . 

15.  of  (lysciilciifonn  enteritis 

B,  pyooyaneus        .         .         .         .  | ,, 

Lepfoflirix   I  > 1 1 f - < • . 1 1 1 

Specii  to  B  \<  i  lima. 

Micrococci. 

( lonococcus 

Diplococcua  intract  llularis  meningitidis 

Micrococcus  of  iiniiiips 

Bacilli. 

B.  anthracia     ......         several  experimental  varieties. 

....,,.,,  f  pseudodiphtheria    1 1 

DipMhenaB.  .       {%hoTtB.(1) 

B.  of  glanders 

Typhoid  1>. 

li.  of  influenza 

Tubercle  bacillus  (perhaps  to  be  placed  i  human   B. 

among  the  streptothrix)        ...         B.  of  ih<-  gallinas. 

I  B.  offish. 
B.  of  leprosy. 
B.  of  pseudotuberculosis. 
B.  of  bubonic  plague. 
B.  of  yellow  fever. 
B.  of  soft  chancre. 
B.  of  tetanus. 

B.  of  gaseous  gangrene      .  .  .  .  B.  of  symptomatic  anthrax. 

B.  of  rheumatism. 
Spirillus  of  recurrent  fever. 
Vibrio  of  Asiatic  cholera. 

The  Infectious  Fungi.  As  already  stated,  infectious  dis< 
may  be  caused  by  plants  more  highly  organized  than  schizophycetae.1 
The  streptothrixse  will  first  be  mentioned.  Of  these  a  dozen  are  at 
present  known,  several  of  which  are  pathogenic.  More  frequently, 
however,  they  induce  local  lesions  only.  There  are  in  this  group  four 
plants  which  are  capable  of  giving  rise  to  genuine  infectious  diseases. 

In  the  first  place,  there  is  Noccirdia  Jarcinosa,  which  produces  a 
malady  known  as  farcina  bovidce.  It  was  discovered  by  Nocard,  who 
at  first  considered  it  to  be  a  cladothrix.  It  causes  in  bovidse  lympha- 
gites  and  suppurating  adenites,  which  are  not  to  be  confounded  with 
true  glanders,  a  disease  from  which  bovida?  are  immune. 

Oospora  asteroides,  discovered  by  Eppinger  (1891)  in  a  cerebral 
abscess,  was  again  found  by  Almquist  in  a  case  of  meningitis,  by. 
Ferre  and  Faguet  in  an  abscess  of  the  brain,  by  Sabrazes  and  Rmere 
in  a  cerebral  abscess  and  in  a  suppurating  infarct  of  the  kidney. 

1  For  the  study  of  these  diseases  consult:  W.  Dubreuihl,  L^s  moisissures  para- 
sitaires  de  l'homme  et  des  animaux  superieurs.  Arch,  de  ni6d.  exper..  1891,  p.  -42S  and 
566.     Blanchard.  Les  parasites  vegetaux.  Traite"  de  path.  gene>ale.  1S96.  t.  ii.p.  811. 


40  lyFECTIOUS  DISEASES. 

Actinomyces  (Nocardia  bovis.  slreptothrix  actinomyces,  oospora 
bovis),  tin1  most  important  agent  of  this  group,  is  pathogenic  for 
both  man  and  various  mammalia,  notably  bovidae.-  It  may  be  con- 
sidered as  the  type  of  higher  agents  capable  of  producing  infectious 
diseases. 

Phycomyces  are  fungi  which  constitute  a  transition  with  the  algae. 
They  include  oomyces  and  zygomyces.  Among  the  former  is  found 
leptomitus,  which  is  pathogenic  for  insects  and  is  also  encountered 
in  man.    In  the  majority  of  instances,  however,  it  is  a  simple  parasite. 

Zygomyces  comprise  the  entomophthorae  and  the  mucedinie.  Fur- 
bringer  reported  two  cases  in  which  the  pulmonary  foci  were  due  to 
mucor  mucedo.  The  case  reported  by  Paltauf1  is  more  interesting: 
The  patient,  a  man,  fifty-two  years  of  age,  succumbed  nine  days 
after  his  admission  into  the  hospital  with  very  serious  general  symp- 
toms: fever,  icterus,  diarrhoea,  tumefaction  of  the  liver,  and  spleen, 
typhoid  state,  and  coma.  At  the  necropsy  there  were  found  intes- 
tinal ulcerations,  foci  of  pneumonia,  cerebral  abscesses,  and  suppu- 
rative laryngitis  and  pharyngitis.  These  various  lesions  were  due  to 
a  parasite  which  appeared  to  be  the  mucor  corymbifer.  Experimen- 
tation further  demonstrated  that  this  vegetable  was  pathogenic  for 
animals  (Lichtheim). 

The  mycomyces  are  fungi  of  a  low  order  comprising  an  important 
group,  viz.,  the  ascomyces.  In  fact,  it  is  in  this  group  that  yeasts 
are  classed.  Experimentation  demonstrated  the  existence  of  a  great 
number  of  yeasts  that  are  pathogenic  for  animals.  A  few  observa- 
tions tend  to  establish  the  same  to  be  true  with  regard  to  man.  This 
subject  will  be  discussed  in  a  separate  chapter. 

Finally,  there  are  the  perisporiacse  which  comprise  aspergillinse. 
These  frequently  produce  lesions  in  the  respiratory  organs  of  birds 
(A.  C.  Mayer,  Robin,  Bouchard,  Hayem,  etc.).  Aspergillus  fumiga- 
tus  may  cause  various  lesions  in  man,  such  as  cutaneous  suppura- 
tions, a  special  form  of  onychomycosis,  suppurations  of  the  cornea, 
or  lesions  in  the  ear  (otomycosis).  In  the  latter  case  other  parasites 
may  also  be  encountered  such  as  aspergillus  nigricans,  aspergillus 
flavescens,  aspergillus  nidulans,  eurotium  repens,  etc. 

Such  are  the  principal  mycoses  observed  in  man.  Their  number 
is  not  considerable,  as  may  be  seen  from  the  following  list  represent- 
ing the  main  vegetable  agents  thus  far  discovered: 

1  Paltauf.  Mvcosi-  mucorina.  Em  Beitrag  zur  Kenntniss  der  menschlicben  Faden- 
pilzerkrankungen.     Virchow's  Archiv,  1885,  Bd.  cii.,  p.  543. 


0  ENEBA  l.  <  'ONSIDERA  TI0N8.  1 1 

Odspora  asteroides  (Streptothrix  and  Nocardia) 
"       bovis  (ad  inomyoee). 
"      madurcB. 

\l  iimr  lit  iimln. 

"      corymbifer. 
oiiliiim  albicans  (Endomycea  albicans,  Vuillemin), 

"  siibtilr. 

Aspergillus  fumigatus. 

]  have  excluded  all  those  vegetable  agents  which  behave  in  man 
as  simple  parasites.  For  the  present  ii  is  sufficienl  to  have  shown 
that  plants  other  than  bacteria  are  capable  of  producing  infections 

in  num. 

Infectious  Protozoa,  [nfections  due  to  protozoa  are  extremely 
frequent  in  the  lower  vertebrates,  fish,  the  batracian,  and  in  verte- 
brates. The  same  is  probably  true  with  regard  to  man  and  higher 
vertebrates,  as  some  recent  researches  tend  to  demonstrate. 

Of  the  four  classes  of  protozoa,  two  only  are  of  interesl  to  us: 
the  rhizopodes  and  the  sporozoa.  Among  the  former  are  t  he  amoebae, 
of  which  three  varieties  are  met  with  in  man.  These  are  designated 
according  to  their  seat,  as  A.  gingivali*,  A.  var/inalis  or  urnyi'iiihili*, 
and  A.  intestinalis.  The  last  is  undoubtedly  the  most  important. 
Numerous  contributions  tend  to  demonstrate  that  it  is  the  causative 
agent  of  an  important  variety  of  dysentery  and  even  of  certain 
abscesses  of  the  liver.  Several  observations  have  been  reported  in 
which  amoeba?  alone  were  found  in  hepatic  suppurations  consecutive 
to  dysentery.  The  author  published,  with  Dr.  Peyrot,  a  case  of  this 
kind.  It  may,  however,  be  presumed  that  ordinary  pyogenic  micro- 
organisms existed  at  a  certain  moment  and  finally  disappeared. 
Experimental  pathology  must,  therefore,  be  resorted  to  in  order  to 
secure  further  information  as  to  the  pathogenic  power  of  amoebae. 
Marchoux  succeeded  in  producing  serious  dysentery  and  hepatic  ab- 
scesses in  cats  by  introducing  dysenteric  dejecta  into  their  digestive 
organs.  These  symptoms  do  not  appear  when  the  same  dejecta  are 
employed  after  subjecting  them  to  a  temperature  which  kills  the 
amoebae  without  affecting  the  accompanying  bacteria. 

The  sporozoa  comprise  several  groups,  among  which  are  found 
myxosporidia,  sarcosporidia,  and  coccidia.  The  importance  of  the 
last-named  group  is  constantly  tending  to  increase.  They  are 
frequently  met  with  in  the  liver  of  rabbits,  where  they  invade  the 
biliary  passages  and  induce  epithelial  and  connective  tissue  pro- 
liferations. Malassez  encountered  forms  resembling  the  so-called 
colloid  cells  of  epithelioma,  the    particular  granula  of    moUnscum 


42  INFECTIOUS  DISEASES. 

contagiosum  and  of  vegetating  follicular  psorospermosis.  These 
results  are  evidently  of  great  importance  in  favor  of  the  coccidian 
theory  of  psorospermosis  and  cancer,  but  the  question  is  far  from 
settled. 

There  has  been  described  under  the  name  coccidium  hominis  a 
parasite  giving  rise  to  intestinal  ulcerations  and  often  to  a  fatal 
cachexia.  The  karyophagus  hominis  of  Podwyssotski  induces  pig- 
mentary atrophy  of  the  hepatic  cells  and  secondarily  gives  rise  to 
proliferation  of  the  interstitial  tissue. 

Sporozoa  also  comprise  the  group  of  gymnosporidia  of  which,  from 
the  standpoint  of  infectious  pathology,  Plasmodium  malaria  is  of 
chief  importance.  As  is  well  known,  this  parasite,  discovered  by 
Laveran  in  1881,  is  the  cause  of  malarial  fever. 

Finally,  should  trichinosis  be  considered  an  infectious  disease? 
The  symptoms  are  evidently  serious  enough  to  deserve  this  denom- 
ination. In  its  first  stage  it  develops  like  a  true  infection,  and,  in 
fact,  it  is  most  frequently  confounded  with  typhoid  fever.  Be  that 
as  it  may,  the  essential  point  established  is  the  fact  that  there  are 
infections  due  to  animal  microbes,  and  if  doubt  as  to  some  instances 
is  still  possible,  there  can  be  none  with  regard  to  malaria — the  disease 
which  all  clinicians  consider  infectious  and  of  which  the  animal  origin 
was  demonstrated  beyond  all  dispute  by  Laveran's  great  discovery. 


(Ml  A  PTE  R    II. 
GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA. 

Polymorphism  <>f  Bacteria,     Variability  of  Their  Different    l  unction        SH  id 

ments,  Pigments,  and  Pathogenic  Properties.  Resistance  of  Bacteria  to  Destructive 
Agents.    Action  of   Mechanical,  Physical,  .'mil  Chemical  Agents.     Action  of  High 

Pressures,     I  1 1  ■ :  1 1 ,    Cold,     l.ii'lil,     Kleet  rieil  v,    Soluble     Sill/   t:inr:fiS,     and      Anti   eptic    ■ 

Difficulty  of  Determinism  in  Microbiology. 

Polymorphism  of   Bacteria.    From  the  very  beginning  of   I >ac- 

teriology  two  contrary  opinions  appeared  as  to  the  value  of  char- 
acters peculiar  to  each  species.  Morphology  was  taken  as  a  basis 
for  classification.  It  was,  therefore,  necessary  to  determine  whether 
the  forms  were  or  were  not  immutable.  Cohn  advocated  monomor- 
phism  of  bacteria,  and  Naegeli  contended  for  polymorphism.  ( hi 
January  22,  1878,  in  a  communication  to  the  Academic  de  M£decine, 
Pasteur  rejected  morphological  classifications,  citing,  as  an  illustra- 
tion, the  example  of  the  septic  vibrio,  which,  he  said,  "according  to 
the  media  in  which  it  is  cultivated,  assumes  shapes,  lengths,  and 
sizes  so  diverse  that  the  observer  might  believe  them  to  be  repre- 
sentatives of  different  species."  In  spite  of  the  exaggerations  of 
Zopf,  polymorphism  made  considerable  progress  and  found  such 
advocates  as  Hueppe,  Koch,  Metchnikoff,  etc. 

In  studying  polymorphism  it  is  necessary  to  distinguish  cultures 
grown  under  eugenesic  conditions  from  those  grown  in  media  or 
under  influences  unfavorable  to  their  development.  In  the  fomer 
instance  morphological  variation  expresses  an  adaptation  to  slight 
or  even  hardly  noticeable  variations  of  environment :  in  the  latter 
case  it  indicates  a  state  of  suffering  and  represents  a  modification  of 
pathological  order. 

Polymorphism  under  Eugenesic  Conditions,  This  must  be  Studied 
in  the  living  animal  and  in  artificial  cultures. 

Pasteur  indicated  the  variations  of  shape  which  the  septic  A'ibrio 
undergoes  in  the  animal  body.  At  the  point  of  inoculation  are  found 
thick  and  short  bacilli;  in  the  peritoneum,  and  particularly  near  the 
surface  of  the  liver,  long,  slender  filaments  are  encountered.  This 
result  may  readily  be  explained:  The  conditions  of  vegetation  are 


44  INFECTIOUS  DISEASES. 

not  the  same  in  the  more  or  less  dense  cellular  tissue  into  which  the 
injection  is  made  and  in  the  peritoneum  where  nothing  hinders  the 
development  of  the  microbe. 

By  sowing. the  same  microbe  on  different  media  dissimilar  forms 
are  often  obtained.  For  instance,  the  bacillus  of  dysenteriform 
enteritis  appears  in  the  infected  organism  in  the  form  of  thick  rods, 
resembling  somewhat  the  bacillus  anthracis,  and  measuring  from  5f- 
to  6/t  in  length  and  from  1.3;"  to  1.5,"  in  breadth.  In  bouillon  they 
are  more  slender.  In  agar-agar  they  do  not  exceed  0.5,«  by  2//  when 
the  culture  is  twenty-four  hours  old;  on  the  days  following  they  are 
not  more  than  l;x  or  even  0.5/*  in  length  and  0.5/*  in  thickness. 
Upon  vegetables  they  are  still  shorter  and  more  slender,  and  a  few 
have  an  oval  shape. 

AVhat  may  seem  more  curious  is  the  fact  that  microbes  may  present 
different  shapes  in  the  same  medium.  In  such  cases  the  change  is 
generally  due  to  old  age,  the  morphological  variations  corresponding 
to  the  various  stages  of  their  evolution.  In  other  instances  a  modi- 
fication of  the  medium  is  to  be  attributed  to  the  life  of  the  micro- 
organisms. The  bacteria  absorb  nutritive  substances  and  produce 
ferments  or  excrete  toxins  which  modify  the  constitution  of  the 
medium.  The  medium  being  thus  modified,  an  adaptation  on  the 
part  of  the  microbes  is  necessitated,  resulting  in  morphological 
changes.  So-called  involution  forms,  which  consist  in  swellings  com- 
parable to  pears,  clubs,  bottles,  etc.,  are  observed,  especially  in  old 
cultures  in  which  the  nutrient  medium  is  exhausted  or  adulterated. 

Polymorphism  of  the  Buccal  Tetracoccus.  In  studying  the  throats  of 
patients  suffering  from  simple  or  scarlatinal  angina  I  have  often 
found  a  microbe  whose  polymorphism  may  lead  to  confusion.  This 
microbe,  analogous  to,  if  not  identical  with,  tetragenus,  is  of  very 
frequent  occurrence  in  the  mouths  of  scarlatinal  patients.  I  have 
discovered  it  in  85  per  cent,  of  such  cases.  The  proportion  is  69  per 
cent,  in  other  sore  throats,  and  52  per  cent,  in  diphtheria.  This 
same  microbe  very  often  inhabits  the  throats  of  normal  individuals 
and  the  buccal  cavity  of  various  animals,  such  as  dogs,  rabbits, 
guinea-pigs,  and  mice.  At  times  it  can  be  recognized  by  direct  exam- 
ination, that  is,  when  it  presents  the  form  of  typical  tetrads  sur- 
rounded with  capsules.  Its  morphological  variations,  however,  are 
considerable,  and  it  not  infrequently  occurs  in  the  form  of  diplococci 
or  is  arranged  in  small  heaps  of  round  elements  in  nowise  charac- 
teristic.    The  polymorphism  of  the  tetracoccus  is  also  marked  in 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERl  1.        |,, 

cultures.    This  morphological  variability  might,  at  fir  t,  lead  to  the 
belief   that  h    is  merely  a  question  of  accidental   contamination. 
The  writer  has  convinced  himself  that  such  is  nol  the  ca  i 
by  certain  procedures  it  is  possible  to  cause  Hie  microbe  in  que 
to  pass  from  the  zoogleic  to  the  tetracoccic  form,  and  vim  <•■ 

The  microbe  of  i  he  author  differs  from  the  classical  tetragenue  not 
only  by  its  polymorphism  hut  also  by  its  action  upon  animals 
Unlike  tetragenus,  it,  is  not  pathogenic  for  rabbits,  and  very  slightly 
so  for  mice.  In  sufficiently  high  doses,  it  produces  vry  strange, 
nervous  disturbances  in  rabbits. 

It  is,  therefore,  difficult  to  determine  whether  t  his  mien, he  ig  iden- 
tical with  the  classical  tetragon  us  or  not.  In  order  not  to  prema- 
turely announce  its  nature,  the  author  proposes  to  provisionally 
designate  it  under  the  name  of  buccal  tetraeoccus  I h/rarorru. 
buccalis).  At  all  events,  the  name  tetraeoccus  is  more  in  harmony 
with  that  of  tetragenus  in  bacteriological  terminology. 

If,  in  spite  of  its  great  frequency  in  cases  of  sore  throats,  this 
microbe  has  not  yet  been  brought  to  notice,  it  is  owing  to  the  fad 
that  it  develops  poorly  upon  serum  and  that  its  polymorphism  has 
caused  it  to  be  confounded  with  other  microbes,  notably  with  t he- 
streptococcus.  This  confusion  can  be  avoided  by  taking  into  account 
the  characters  above  indicated.  In  doubtful  cases  it  is  well  to  trans- 
fer a  colony  to  gelatin.  This  medium,  which  is  rapidly  liquefied  by 
the  streptococcus,  remains  solid  under  the  action  of  the  tetracoccu.-. 

Other  examples  might  be  quoted,  but  those  above  referred  to 
suffice  to  show  how  numerous  are  the  morphological  variations  pre- 
sented by  bacteria  in  the  course  of  their  development  in  the  same 
medium.  Analogous  differences  are  also  observed  according  as  solid 
or  liquid  culture  media  are  employed.  In  liquid  media  the  microbes 
generally  grow  in  length  and  group  themselves  in  a  different  manner. 
This  is  not  surprising.  The  stud}7  of  plants  of  low  organization, 
'notably  alga?,  furnishes  similar  examples.  Not  to  leave  the  field  of 
pathogenic  agents,  it  will  suffice  to  recall  oidium  albican*.  According 
as  this  plant  is  grown  in  agar-agar  or  in  bouillon,  oval  or  the  fila- 
mentous forms  predominate. 

Polymorphism  under  Dysgenesic  Conditions.  The  variations  mani- 
fested b}7  bacteria  are  still  more  curious  when  the  latter  are  placed 
under  conditions  unfavorable  to  their  development.  In  this  connec- 
tion it  will  be  interesting  to  examine  the  influence  of  mechanical 
agents,  and  to  determine,  for  instance,  whether  morphology  is  the 


46  INFECTIOUS  DISEASES. 

same  when  the  culture  is  undisturbed  or  is  agitated.  As  to  physical 
agents,  the  role  of  heat  alone  has  thus  far  been  studied.  It  is  known 
that  the  finest  involution  forms  are  obtained  by  placing  the  cultures 
in  overheated  media.  The  role  of  chemical  agents  has  received  more 
attention.  Drs.  Guignard  and  Charrin  full}''  demonstrated  the  pro- 
found modifications  presented  by  the  bacillus  pyocyaneus  when  cul- 
tivated in  media  to  which  antiseptic  substances  have  been  added. 
The  bacillus  then  lengthens  and  assumes  a  filamentous  form,  or  it 
rolls  up  into  the  shape  of  spirilla,  or  its  size  is  reduced  to  such  an 
extent  as  to  resemble  micrococci.  These  curious  results  were  con- 
firmed b}7,  Wasserzug's  researches. 

Under  the  same  conditions  many  other  microbes  present  morpho- 
logical variations.  In  this  respect  the  most  remarkable  microbe  is 
the  B.  prodigiosus.  When  grown  upon  gelatin  containing  2.5  to  3 
per  cent,  of  boric  acid,  it  produces  a  magnificent  spirilla  having  ten, 
twelve,  and  even  sixteen  or  twenty  turns;  each  turn  of  the  spiral 
has  a  length  of  about  1.5//;  then  on  the  fourth  day  involution 
forms  appear  which  occupy  the  central  part  or  the  end  of  the 
spiral. 

With  the  atypical  variety  I  obtained  in  the  same  medium  filaments 
varying  in  length  from  15//  to  120//  and  even  180//.  Toward  the 
tenth  day  these  filaments  became  segmented  and  gave  rise  to  motile 
bacilli;  at  the  same  time  involution  forms  appeared. 

If  a  portion  of  these  peculiar  cultures  is  transferred  to  the  usual 
media,  colonies  are  obtained  in  which  the  microbes  resume  their 
normal  form.  The  modifications  imposed  by  antiseptics  are,  there- 
fore, transitory.  Wasserzug  believed,  however,  that  he  had  obtained 
an  actual  transformation  and  fixation  of  new  characters.  In  reality, 
it  is  not  possible  to  create  by  these  procedures  anything  more  than 
varieties  comparable  to  the  varieties  observed  in  higher  beings.  In 
other  words,  we  cannot  transform  the  species. 

As  to  the  capsules  which  surround  certain  microbes,  it  must  be 
stated  that  they  are  scarcely  of  any  morphological  and  diagnostic 
importance,  since  they  are  quite  inconstant. 

Variability  of  the  Functions  of  Bacteria.  The  experimenter 
may  produce  functional  variations  in  microbes.  He  can  modify 
their  mode  of  reproduction,  and  by  means  of  chemical  agents  he  can 
create  asporogenic  varieties.  Such,  for  instance,  is  the  case  with 
the  bacillus  anthracis. 

Pasteur  believed   it  was   possible   to   characterize   and   classify 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA.        17 

microbes  by  a  study  of  their  action  upon  fermentable  sub  tai 
Eowever,  in  this  respect,  also,  the  results  are  nol  con  tant.  For 
instance,  let  us  examine  the  action  of  the  colon  bacillus  upon  milk. 
The  typical  examples  of  this  microbe  coagulate  milk  because  they 
attack  the  lactose,  producing  fermentation,  and  thm  rendering  the 
medium  acid.  There  are,  however,  other  varieties  of  colon  bacilli,  the 
paracolon  bacillus  of  Gilbert,  which  do  no1  coagulate  milk.  The 
author  has  observed  a  colon  bacillus  derived  from  a  gangrenous 
pleurisy  which  did  nol  at  first  acl  upon  milk.  On  cultivating  it  in 
inert  media,  it  was  noticed  that  the  medium  was  slowly  rendered 
acid.  It  took  a  week  to  produce  a  little  deposit  of  casein;  two 
months  later  the  same  microbe  completely  coagulated  milk  in 
twenty-four  hours.  Here,  therefore,  is  a  variety  that  passed  from 
the  group  of  paracolon  bacilli  to  that  of  the  typical  colon  bacillus. 

Similar  results  are  obtained  with  yeasts.  The  transformation  of 
sugar  varies  according  to  the  aeration  of  the  medium.  The  yeast 
plant,  when  living  in  the  air,  consumes  free  oxygen,  multiplies  rapidly 
and  oxidizes  the  sugar  almost  without  forming  any  alcohol.  In  its 
anaerobic  life  it  is  compelled  to  abstract  oxygen  from  the  sugar, 
which  it  then  transforms  into  alcohol  and  carbonic  acid. 

Bacterial  Ferments.  The  action  of  microbes  upon  sugar  and  albu- 
minoid substances  is  also  variable  and  differs  according  to  the  species 
employed,  the  age  of  the  cultures,  the  nature  of  the  medium,  etc. 
Vignal  called  attention  to  the  important  role  of  pabulum  furnished 
to  bacteria.  By  adding  certain  substances  to  the  culture  medium  the 
microbe  can  be  made  to  secrete  ferments  which  affect  the  substances 
introduced.  There  is  only  one  secretion  which  seems  never  to  un- 
dergo any  variation,  namely,  that  ferment  which  peptonizes  gelatin. 
It  is  known  that  many  authors  consider  the  liquefaction  of  this  sub- 
stance as  of  importance  in  bacterial  diagnosis.  It  is,  in  fact,  one  of 
the  most  stable  properties  and,  consequently,  one  of  those  which  are 
of  considerable  importance  in  classification. 

Variability  of  Bacterial  Pigments.  Aside  from  the  ferments, 
bacteria  secrete  various  products,  some  of  which  may  serve  for  iden- 
tification of  the  species.  Pigments  are  the  most  important  of  such 
products.  A  great  number  of  microbes  color  the  culture  media  yel- 
low, red,  green,  and  more  rarely  blue  or  violet.  This  chromogenic 
function  is  extremely  variable.  Certain  microbes  produce  pigments 
in  certain  media.  Thus  the  bacillus  of  glanders  and  the  colon  bacillus 
yield  patches  of  a  deep  brown  color  when  grown  upon  potatoes.   The 


48  ISFECTIO  US  DISEASES. 

colon  bacillus,  unlike  the  typical  bacillus,  produces  a  superb  green 
color  on  slices  of  artichoke. 

Under  various  circumstances  certain  chromogenic  microbes  may 
cease  to  produce  pigment.  For  instance,  B.  prodigiosus  when  grown 
in  agar-agar  secretes  a  beautiful  red  pigment.  If  transferred  to 
bouillon  it  does  not  color  the  medium;  or  to  speak  more  accurately, 
certain  cultures  do  not  color  bouillon,  while  others  do  color  it  red 
or  rose. 

By  modifying  the  physical  conditions  of  development,  the  produc- 
tion of  pigments  may  easily  be  modified.  Schottelius  has  shown  that 
B.  prodigiosus  produces  very  little,  if  any,  pigment,  even  in  agar- 
agar,  if  the  culture  is  kept  in  an  incubator  at  a  temperature  of 
100.4  F.  (38°  C.)  or  102.02°  F.  (39°  C).  Under  these  conditions  the 
majority  of  colonies  are  white.  If,  however,  this  colorless  culture  be 
grown  at  a  lower  temperature,  it  becomes  rose-colored,  then  red. 

Analogous  results  are  obtained  by  preventing  the  access  of  air. 
The  author  has  shown  that  a  culture  of  B.  prodigiosus  grown  under 
oil  remains  colorless.  When  it  is  subsequently  brought  in  free  con- 
tact with  air,  color  appears. 

The  most  interesting  modifications  are  those  caused  by  addition 
of  soluble  or  insoluble  antiseptics  to  the  culture  bouillon.1  Several 
of  these  substances  first  act  upon  the  function  of  the  microbe.  In 
small  amounts  they  hinder  or  arrest  the  development  of  coloring 
substance;  in  larger  amounts,  they  hinder  or  arrest  development; 
finally,  their  action  may  still  be  more  marked  and  may  kill  the 
microbe. 

In  pursuing  the  researches  on  chromogenic  bacteria  I  was  able  to 
prevent  the  production  of  pigment  in  B.  prodigiosus  by  adding  boric 
acid  to  the  culture:  2.5  to  5  per  1000  suffices.  Staphylococcus 
aureus  produces  white  colonies  when  cultivated  in  gelose  containing 
3  per  1000  iodoform,  or  0.6  per  1000  of  carbolic  acid.  These  amounts 
are  close  to  sterilizing  quantities,  which  are  3.5  per  1000  for  the 
former  substance,  and  0.8  per  1000  for  the  latter.  Finally,  I  have 
noted  that  extremely  small  amounts  of  antiseptics  stimulate  rather 
than  hinder  the  chromogenic  function.  In  the  presence  of  a  trace 
of  corrosive  sublimate  B.  prodigiosus  produces  a  very  intense  red 
pigment. 

These  experiments  are  susceptible  of  infinite  variations.    The  few 

1  Charrin  et  Roger.  Des  modifications  qu'on  peut  provoquer  dans  les  fonctions 
d'un  microbe  chromogene.     Soc.  de  biologie,  Oct.  29,  1887. 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA.       \u 

illustrations  above;  referred  to  suffice  to  show  the  influence  of  the 
surrounding  medium  upon  the  chromogenic  function  of  microbi 

Variability  of  Pathogenic  Properties.  Since  the  research) 
Pasteur,  ii  is  known  thai  microbic  virulence  may  very  notably  be 
modified.  II'  a  pathogenic  microbe  is  for  some  time  cultivated  in 
artificial  media  its  virulence  gradually  diminishes  and  ii  sometimes 
falls  to  the  rank  of  a  saprophyte.  Reciprocally,  by  passing  ii  suc- 
cessively through  living  animals,  it  is  possible  to  accustom  the 
microbe  to  a  parasitic  life;  in  oilier  words,  it  become-  exalted,  and 
in  many  cases  quite  considerably.  Pasteur's  researches  further 
established  that  a  microbe  thai  has  been  exalted  for  one  animal 
species  may  be  found  weakened  for  another.  It  is  also  possible  to 
modify  virulence  by  making  the  cultures  under  special  condition.-, 
notably  by  subjecting  them  to  high  degrees  of  temperature,  com- 
pressed oxygen,  and  chemical  substances.  These  various  pro© 
enable  us  to  create  species  of  definite  virulent  power,  or,  as  is  said, 
fixed  viruses.  The  bacillus  anthracis,  for  instance,  may  be  culti- 
vated in  such  a  manner  as  to  be  rendered  incapable  of  killing  the 
rabbit  or  of  exerting  any  action  upon  even  the  adult  guinea-pig;  it 
can  kill  only  the  young  guinea-pigs.  By  progressively  graduated 
passages  through  a  living  organism  it  may  recover  its  virulence. 

It  is,  therefore,  possible  profoundly  to  modify  the  properties  of 
bacteria,  viz.,  to  suppress  their  sporogenic,  chromogenic,  and  virulent 
powers.  Thus  new  varieties  differing  considerably  from  the  original 
stock  and  not  always  surely  convertible  into  it  may  be  created.  The 
functions  thus  abolished,  however,  are  fonctions  de  luxe,  since,  not- 
withstanding these  modifications,  vegetation  and  reproduction  may 
easily  be  accomplished.  It  is  none  the  less  interesting  to  note  how 
contingent  are  the  properties  of  microbes,  and  how  difficult  the  deter- 
mination of  the  species.  The  uncertainty  of  bacteriological  diagnosis 
is  so  great  that  the  same  microbe  has  not  infrequently  been  described 
under  the  most  varied  names.  This  variability  in  the  characters  of 
microbes  is  also  referable  to  the  fact  that  cultures  are  not  and  can 
never  be  uniform.  For  instance,  if  a  colony  of  bacillus  prodigiosus 
is  diluted  with  a  large  amount  of  liquid  and  sown  on  plates,  some 
of  the  colonies  which  develop  will  be  red.  others  rose-colored,  and 
still  others  white.  If  a  colony  apparently  uniform — red  or  white — 
is  diluted  and  sown,  it  will  again  produce  dissimilar  colonies.  This 
simple  experiment  clearly  demonstrates  that  all  the  microbes  develop- 
ing from  the  same  stock  are  not  equally  capable  of  secreting  pigment. 

4 


50  INFECTIOUS  DISEASES. 

The  results  are  identical,  though  less  readily  conceivable,  with 
regard  to  the  pathogenic  function.  All  the  individuals  of  the  same 
culture  do  not  possess  the  same  power.  It  must,  however,  be  recog- 
nized that  by  taking  certain  precautions  we  can  diminish  the  differ- 
ences, though  we  are  unable  to  make  them  altogether  disappear. 
Hence  the  necessity  of  carefully  taking  into  consideration  the  sources 
of  error  connected  with  these  experiments. 

This  variability  of  the  elements  contained  in  a  culture  fluid  explains 
why  when  this  fluid  is  submitted  to  the  action  of  some  destructive 
cause  the  number  of  microbes  is  first  diminished,  but  the  medium 
is  not  completely  sterilized.  Take,  for  instance,  some  pure  bouillon 
culture  and  count  the  microbes  by  means  of  plates,  and  then  submit 
the  culture  to  the  action  of  some  destructive  agent.  As  all  the 
elements  are  subjected  to  the  same  harmful  influence,  simultaneous 
decline  of  vegetation,  weakening  of  functions,  and  final  destruction 
are  expected.  Such,  however,  is  not  the  case.  It  will  be  seen  that 
the  number  of  colonies  obtained  on  the  plates  diminishes  successively, 
which  proves  that  certain  microbes,  of  weaker  resistance,  were  the 
first  to  disappear;  but  others  remain  which,  unless  the  conditions 
are  too  unfavorable,  will  overcome  the  dysgenesic  conditions  and 
become  more  or  less  perfectly  accustomed  to  them.  There  occurs, 
therefore,  a  sort  of  natural  selection. 

Influence  of  Various  External  Agents  upon  Bacteria. 

Influence  of  Mechanical  Agents.  The  causes  which  arrest  the 
development  of  and  destroy  microbes  are  mechanical,  physical,  or 
chemical. 

The  mechanical  causes  are  represented  by  the  movement  of  culture 
fluids.  If  the  fluid  is  agitated  the  microbes  do  not  develop  or  develop 
badly,  but  the  fluid  is  not  rendered  sterile.  By  means  of  a  simple 
apparatus  invented  by  Dr.  Gozard,  I  learned  that  repeated  shocks 
in  nowise  affect  the  life  of  microbes.  The  microbes  experimented 
upon — staphylococcus  aureus,  colon  bacillus,  streptococcus  of  ery- 
sipelas, sporulating  or  non-sporulating  bacillus  anthracis — were  in  no 
way  affected  by  the  mechanical  action. 

Action  of  High  Pressures.  The  influence  of  pressure  has  been 
studied  by  various  experimenters.  The  somewhat  dissimilar  results 
are  referable  to  the  diversity  of  the  methods  employed.  The  experi- 
ments of  Regnard,  Dubois,  Certes,  and  Cochin  demonstrated  that 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA. 

low  beings  resist  very  high  pressure.  The  beer  yea  I  i  capable  of 
bearing  300  to  loo  atmospheres  for  several  days  without  being  &b- 
stroyed.  When  submitted  to  L000  atmospheres  lor  one,  hour  it 
becomes  torpid  and,  an  hour  later,  ii  is  again  capable  of  producing 
fermentation  of  sugar.  The  same  is  true  of  algae  and  infusoria  which 
have  been  subjected  to  a  pressure  of  600  atmospheres.  The  algae 
germinate  only  after  a  week;  the  protozoa  remain  for  some  time 
motionless  and  then  resume  their  movements,  llegnard  further 
learned  that  relatively  higher  organisms  such  as  mollusks,  crustac 
and  leeches  can  endure  500  or  000  atmospheres  without,  perishing. 

As  to  bacteria,  the  effects  of  pressure  vary  considerably,  according 
to  experimental  conditions.  In  fact,  it  seems  demonstrated  that 
compressed  gases  exert  a  very  noxious  influence  upon  several  mi- 
crobic  species.  According  to  P.  Bert,  oxygen,  under  a  pressure  of 
from  8  to  10  atmospheres,  arrests  putrefaction.  The  atmospheric 
air,  under  the  same  conditions,  produces  an  analogous  but  less  intense 
effect.  In  studying  the  bacillus  anthracis,  Prof.  Chauveau  showed 
that  oxygen  at  12  atmospheres  weakens  the  vitality  of  this  microbe 
and  at  the  same  time  diminishes  its  virulence  to  such  an  extent  as 
to  transform  it  into  a  vaccine.  Carbonic  acid  under  pressure  is 
equally  harmful  to  bacteria.  C.  Fraenkel  recognized  that  seltzer 
water  contains  no  microbes.  All  species  do  not,  of  course,  possess 
the  same  power  of  resistance.  Hence  the  apparently  contradictory 
results  obtained  by  Sabrazes  and  Bazin. 

.  The  effect  of  800  or  1000  atmospheres  upon  the  four  microbes 
(experimented  upon  in  the  author's  first  researches1)  proving  nega- 
tive, the  author  thought  it  important  to  study  the  action  of  still 
greater  pressures.  He  experimented  with  an  apparatus  by  means  of 
which  the  pressure  could  be  raised  to  2903  atmospheres,  the  cultures, 
as  usual,  being  enclosed  in  rubber  tubes.  Since,  however,  the  high 
pressure  caused  the  water  to  filter  through  the  walls  of  the  apparatus, 
the  author  filled  the  cylinder,  in  which  the  tubes  were  placed,  with 
oil.  A  special  contrivance,  set  in  motion  by  means  of  a  motor  engine, 
raises  the  pressure  gradually,  so  that  it  takes  ten  minutes  to  attain 
2903  atmospheres.  This  pressure,  the  highest  that  can  actually  be 
obtained,  is  kept  up  for  two  minutes:  it  is  not  possible  to  further 
prolong  the  experiment  without  danger  to  the  apparatus.  The 
pressure  is  then  allowed  to  fall  to  the  normal:  this  descent  is  rapid, 

1  Roger.    Action  of  High  Pressures  upon  Some  Bacteria.    Comp.  Rend,  de  lAcademie 
des  Sciences,  Dec.  3,  1S94;  Arch,  de  phys..  Jan.  1.  1S95. 


52  ISFECTIOUS  DISEASES. 

as  it  lasts  but  ten  seconds.  The  latter  fact  is  of  considerable  impor- 
tance, for  perhaps  some  of  the  effects  obtained  may  be  due  to  de- 
compression. 

Under  these  conditions  the  colon  bacillus  and  staphylococcus 
aureus  have  hitherto  suffered  no  modification;  their  cultures  were 
as  luxuriant  after  as  before  the  experiment.  Their  functions  were 
not  even  disturbed,  since  the  staphylococcus  preserved  its  chromo- 
genic  power. 

The  streptococcus  was  sown  in  agar-agar  before  and  after  com- 
pression. The  tubes  were  placed  in  the  incubator  at  6  p.m.  and 
examined  at  9  a.m.  the  following  day.  Those  which  had  received 
the  normal  cultures  were  covered  with  colonies;  the  others  showed 
no  growth.  In  the  evening,  however,  they  presented  colonies  one- 
third  less  numerous  than  the  control  tubes.  Apart  from  these 
numerical  differences,  which  remained  the  same  the  following  days, 
there  was  no  appreciable  modification  either  in  the  appearance  of 
the  colonies  or  in  the  form  of  the  microbes. 

In  conjunction  with  the  culture  experiments  inoculations  were 
practised  upon  rabbits.  Ten  drops  of  the  culture  were  introduced 
under  the  skin  of  the  ear.  Two  days  after  the  rabbits  which  had 
received  the  streptococcus  subjected  to  compression  were  attacked 
by  erysipelas  of  the  ear.  The  affection  grew  worse  on  the  following 
days,  then  began  to  subside,  and  disappeared  on  the  tenth  or 
eleventh  day.  The  controls  presented  no  local  lesion;  they  suc- 
cumbed to  a  general  infection  five  or  six  clays  after  the  inoculation.. 

A  pressure  of  2903  atmospheres  (about  3000  kilogrammes  per 
square  centimetre)  is,  therefore,  capable  of  killing  a  few  streptococci. 
It  induces  in  those  which  survive  a  sort  of  torpidity  as  expressed  by 
a  notable  delay  in  development,  and,  what  is  of  greater  consequence, 
it  diminishes  their  virulence  to  such  an  extent  as  to  leave  them  the 
power  to  produce  only  a  local  and  rapidly  curable  lesion. 

The  effects  of  pressure  upon  the  bacillus  anthracis  are  analogous 
to  the  above. 

It  may,  however,  be  questioned  whether  the  effects  observed  with 
the  streptococcus  and  the  bacillus  anthracis  are  due  to  the  increase 
of  pressure.  The  rise  of  temperature  caused  by  compression  of  the 
fluids  may,  perhaps,  account  for  all  these  phenomena.  Commandant 
Meillet,  who  has  studied  this  problem,  calculated  that  under  a  press- 
ure of  2903  atmospheres  (3000  kilogrammes)  the  rise  of  temperature 
was  only  9.54°  F.  (5.3°  C).    This  is  rather  too  high  a  figure,  as  it 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA 

assumes  that  all  the  force  is  transformed  into  heat.    The  thermal 
effect  cannot,  therefore,  explain  the  action  of  pre  sure. 

In  order,  however,  to  influence  the  life  or  function*  of  microbe 
enormous  pressures  far  in  excess  of  actual  cosmic  variations  musl 
be  employed,  since  the  pressure  at  the  bottom  of  the  sea  i  far  less 
(500  or  600  kilogrammes).  Consequently,  if  may  I"-  Btated  thai 
changes  of  atmospheric  pressure  occurring  on  our  globe  play  no  r61e 
in  the  modification  of  the  virulence  of  the  microbes  surrounding  u  . 

Action  of  Physical  Agents  on  Bacteria.  V  i  well  known. 
physical  agents,  especially  heat  and  light,  exerl  a  harmful  influence 
upon  bacteria. 

Action  of  Heat.  Heat  is  daily  employed  for  purposes  of  steriliza- 
tion. All  bacteria,  however,  are  not  destroyed  at  the  same  tempera- 
ture. There  are  some  that  can  live,  develop,  and  multiply  between 
158°  and  165°  F.  (70°  and  74°  C).  Globig  found  in  the  soil  thirty 
species  living  between  122°  and  158°  F.  (50°  and  70°  C).  Miquel, 
Olivier,  Rabinowitsch,  and  Macfayden  studied  the  thermophilic 
microbes  found  in  hot  spring  waters  and  notably  in  sulphurous 
waters. 

For  the  same  bacterial  species,  sensitiveness  to  heat  varies  accord- 
ing to  several  conditions.  The  spores  are  more  resistant  than  the 
adult  forms.  Heat  is  more  destructive  to  the  microbes  when  the 
latter  are  contained  in  a  fluid  medium  than  when  in  a  desiccated 
state.  Finally,  the  action  of  heat  is  considerably  increased  by 
the  presence  of  air  which  produces  oxidation  unfavorable  to  bac- 
teria. 

Immersed  in  water  at  140°  F.  (60°  C.)  the  tubercle  bacillus  lives 
for  twenty  minutes;  and  in  water  at  158°  F.  (70°  C),  for  ten  minutes. 
Boiling  water  at  212°  F.  (100°  C.)  kills  it  in  five  minutes.  The 
same  bacillus  is  capable  of  resisting  a  dry  heat  of  212°  F.  for  several 
hours. 

The  influence  of  air  is  shown  by  Dr.  Roux's  experiments.  When 
subjected  to  the  combined  action  of  air  and  a  temperature  of  15S°  F. 
(70°  C.)  the  spores  of  bacillus  anthrads  die  in  sixty  hours:  when 
protected  from  air  they  live  one  hundred  and  sixty-five  hours. 

Resistance  to  cold  is  far  more  considerable.  Ice  contains  numerous 
microbes.  Dr.  Pictet  subjected  bacteria  to  temperatures  of  — 166°  F. 
(—110°  C.)  and  even  —328°  F.  (—200°  C.)  without  being  able  to 
kill  them.  Prof.  D'Arsonval  immersed  some  in  liquefied  air  with- 
out causing  them  to  lose  their  power  to  vegetate. 


54  ISFECTIOUS  DISEASES. 

Action  of  Light.  The  influence  of  sunlight  is  at  least  as  important 
as  that  of  heat.  It  may  easily  be  proved  by  the  following  experi- 
ment: A  few  drops  of  an  anthrax  culture  are  spread  upon  a  gelatin 
plate,  which  is  then  covered  with  a  glass  upon  which  pieces  of  black 
paper  are  pasted.  When  exposed  to  light,  development  takes  place 
in  the  protected  parts,  and  the  bacteria  exactly  reproduce  the  designs 
figured  by  the  pieces  of  black  paper. 

This  influence  of  sunlight  is  constantly  at  work  in  nature.  Bacteria 
are  speedily  destroyed  at  the  surface  of  the  soil,  while  at  twenty 
inches  below  the  surface  they  find  excellent  conditions  of  resistance, 
and  may  retain  their  vitality  for  more  than  five  months. 

The  results  are  similar  for  bacteria  immersed  in  water. 

Pansini  introduced  a  few  drops  of  an  asporogenic  anthrax  culture 
into  water  which  he  then  subjected  to  the  action  of  the  sun.  The 
number  of  bacteria  was  primarily  2520  per  cubic  centimetre.  At 
the  end  of  twenty  minutes  the  number  was  reduced  to  130,  and  at 
the  end  of  half  an  hour  to  44  per  cubic  centimetre.  After  forty-five 
minutes  there  were  none  to  be  found. 

Procaccini  took  sewer  water  containing  300,000  to  420,000  bac- 
teria per  cubic  centimetre  and  subjected  it  to  solar  influence.  At 
the  end  of  the  day  the  water  was  sterile. 

The  following  is  another  experiment  made  under  perfect  condi- 
tions: The  water  of  the  Isar,  before  its  entrance  into  the  city  of 
Munich,  was  examined  by  Buchner  at  different  hours  of  the  day. 
The  highest  figure  was  found  at  4  a.m.,  as  bacteria  had  increased 
during  the  night,  and  their  number  then  reached  520  per  cubic  cen- 
timetre. The  minimum  was  observed  at  8  p.m.  Exposed  to  the  sun 
all  day,  the  water  contained  no  more  than  five  bacteria  per  cubic 
centimetre. 

The  experiments  of  Marshall  Ward  tend  to  prove  that  light  acts 
directly  upon  the  anthrax  spores,  and  that  its  action  is  inhibited 
when  the  plant  is  protected  by  means  of  a  screen  intercepting  the 
blue  and  violet  rays.  Thus,  as  Downes,  Blunt,  Arloing,  Buchner, 
and  Frankland  had  already  seen,  it  is  the  most  refrangible  rays  which 
possess  germicidal  power.  The  orange  and  red  rays  do  not  disturb 
the  development  of  bacteria. 

As  in  the  case  of  heat,  the  action  of  light  is  favored  by  the  presence 
of  air.  Dr.  Momont  demonstrated  that  anthrax  spores  perish  after 
forty-eight  hours  of  insolation  when  they  are  in  contact  with  air. 
In  vacuo  they  live  for  one  hundred  and  ten  hours. 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA 

Light  modifies  the  functions  of  bacteria  at  the  ame  time  that  it 
affects  their  vitality.  Anthrax  is  attenuated  under  it  influence.  The 
red  bacillus  of  Kiel  ceases  fco  produce  pigment,  at  times  permanently, 
so  that  if  it  is  sown  in  the  shade,  it  does  not  recover  its  chromogenic 
function. 

The  study  of  the  other  physical  agents  a  this  connection 
matter  of  considerable  difficulty.  Hence,  in  the  old  experiment* 
upon  the  effects  of  electricity  the  currents  employed  produced  heat 
and  electrolysis.  The  germicidal  action  was  due,  therefore,  to  ther- 
mal  or  chemical  modifications.  Those  experimenters  who  have  taken 
cognizance  of  these  sources  of  error  have  not  been  able  to  detect  any 
direct  action  of  electricity  upon  bacteria. 

Action  of  Chemical  Agents.  Those  chemical  agents  which  are 
capable  of  unfavorably  affecting  bacteria  are  called  antiseptic  agents. 
Among  gases  there  is,  for  instance,  ozone,  of  which,  as  is  known, 
great  quantities  are  often  found  in  the  atmosphere.  Its  action  is 
very  energetic,  at  least  upon  the  adult  forms.  The  asporogenic 
anthrax  bacillus  is  killed  under  its  influence  in  five  hours,  but  the 
spores  perish  only  after  three  or  four  days. 

The  antiseptics  properly  so  called  possess  the  very  curious  property 
of  stimulating  the  functions  of  bacteria  when  employed  in  minute 
quantities.  Under  their  influence  the  chromogenic  microbes  produce 
a  greater  amount  of  pigment.  When  the  amount  of  the  antiseptic 
is  raised  the  chromogenic  power  declines  and  even  disappears. 
Vegetation  then  becomes  slow,  is  arrested,  and  finally  the  microbe 
perishes. 

Carbolic  acid  is  one  of  those  most  frequently  employed.  In  solu- 
tions of  1  per  cent,  it  kills  the  asporogenic  anthrax  bacillus  in  ten 
seconds.  If  the  microbe  is  spore-bearing,  life  persists  for  thirty-seven 
days  in  a  solution  five  times  stronger. 

In  order  to  promote  the  action  of  antiseptics,  it  is  advisable  to 
raise  the  temperature  of  the  medium.  Here  is  a  fact  of  consider- 
able importance  from  a  practical  point  of  view.  For  purposes  of 
disinfection,  warm  solutions  should  be  used.  Thus,  while  anthrax 
spores  resist  a  5  per  cent,  solution  of  carbolic  acid  at  ordinary 
temperature,  they  perish  in  the  same  solution  in  two  hours  if  the 
temperature  reaches  131°  F.  (55°  C),  and  in  three  minutes  if  it  rises 
to  134.6°  F.  (57°  C). 


56  I SFECTIOUS  DISEASES. 

Determination  of  Pathogenic  Species. 

In  order  for  a  microbe  to  be  considered  as  the  true  cause  of  a  dis- 
ease it  must.. it  is  said,  fulfil  the  following  four  conditions:  it  must 
be  present  in  all  individuals  suffering  from  the  disease;  it  must  not 
be  found  in  other  diseases;  it  must  be  possible  to  isolate  and  cultivate 
it :  and,  finally,  it  must  reproduce  the  disease  by  inoculation  of  its 
cultures. 

These  rules  are  excellent,  but  cannot  be  accepted  as  absolutely 
exact,  and  they  therefore  require  some  discussion. 

The  first  precept  is,  perhaps,  the  most  immutable,  and  would  seem 
to  admit  of  no  exception.  In  certain  cases,  however,  the  search  for 
microbes  may  be  fruitless  without  impairing  the  value  of  previous 
positive  findings.  The  pathogenic  agent  is  not  necessarily  dissem- 
inated throughout  the  organism.  It  is,  therefore,  possible  to  over- 
look it  if  cultures  are  not  prepared  from  every  tissue  and  fluid.  Even 
in  those  cases  in  which  numerous  cultures  are  made  the  result  may 
be  negative  for  the  reason  that  the  pathogenic  agent  is  destroyed 
before  the  time  of  examination,  having  left  lesions  or  a  special 
cachexia.  Suppurations  originated  by  microbes  persist  long  after  the 
extinction  of  the  microbes.  Analogous  facts  are  matters  of  daily 
observation  in  experimental  pathology.  We  inoculate  a  mild  virus, 
the  animal  dies  after  a  considerable  length  of  time.  At  that  moment 
the  most  minute  examination,  the  most  exhaustive  series  of  cultures 
fail  to  reveal  the  microbe  introduced.  It  has  perished,  but  the  post- 
infectious events  have  followed  their  course  to  a  fatal  termination. 

Another  cause  of  error  results  from  the  fact  that  the  principal 
microbe  may  be  accompanied  by,  and  even  be  lost  among,  other 
microbes.  Necropsy  is  generally  practised  too  late  to  give  reliable 
results,  for  during  the  agony  various  species  of  microbes,  particularly 
the  colon  bacillus,  pass  from  the  intestine  into  the  viscera,  fluids,  and 
tissues,  and  it  is  these  microbes  wdiich  are  found  at  the  necropsy. 
These  germs  develop  in  artificial  media  more  readily  than  the  specific 
microbes,  and  if  they  are  of  the  pathogenic  class,  as  is  the  colon 
bacillus,  they  may  readily  be  mistaken  for  the  cause  of  infection. 

Even  when  examination  is  made  during  life  microbic  associations 
are  apt  to  lead  to  error.  In  diphtheria,  for  instance,  it  is  quite 
exceptional  to  meet  with  a  case  free  from  such  associations.  It  is 
not  strictly  correct  to  speak  of  pure  diphtheria.  Those  cases  in  which 
inoculation  into  serum  gives  rise,  at  the  end  of  fifteen  hours,  to  no 


GENERAL  CHARACTERS  OF  PATHOGENIC  BAOTERl  I 

other  than  the  colonies  of  Loeffier's  bacilhu  arethu  de  ignated.  If, 
however,  the  same  culture  is  examined  after  a  fein  da}  .  a  greal 
number  of  other  microbes  are  found.  In  certain  instance  "i  true 
diphtheria  I  he  specific  microbe  may  be  absent ,  having  been  di 

by  common  bacteria. 

Analogous  statements  may  be  made  with  reference  to  cutanea 
diseases.  Secondary  infections  play  a  very  greal  r61e  in  all  affections 
of  the  skin  and  in  eruptive  fevers.  For  instance,  al  a  certain  period, 
pustules  of  variola  always  contain  a  greal  number  of  microbes  which 
have  nothing  to  do  with  the  cause  of  the  disease.  These  common 
bacteria,  may  at  limes  even  penetrate  into  the  organism  and  consid- 
erably embarrass  bacteriological  study. 

There  are  other  clinical  types  in  which  microbic  association  is  still 
more  important,  not  to  say  indispensable.  Such  is  the  case  in  tet- 
anus. The  bacillus  of  Nicolaier  is  incapable  of  developing  in  healthy 
tissues.  In  order  to  be  able  to  act,  it  requires  the  assistance  of 
auxiliaries  to  reduce  the  resistance  of  the  animal  organism.  The 
morbid  focus,  therefore,  contains  various  microbes,  but  the  tetanus 
bacillus  alone  secretes  the  poisons  which  reproduce  in  animals  the 
characteristic  phenomena  of  the  disease. 

Finally,  in  certain  cases,  the  morbid  centre  contains  several  bac- 
teria endowed  with  wellnigh  similar  properties.  In  such  instances 
the  doubt  as  to  the  respective  share  of  each  of  them  is  unavoidable 
and  legitimate. 

The  third  law  which  has  been  cited  will  not  detain  us  long.  It  is 
now  recognized  as  a  common  truth  that  the  relations  existing  between 
pathogenic  agents  and  diseases  are  not  such  as  they  have  been 
defined.  It  is  scarcely  necessary  to  recall  that  the  streptococcus 
sometimes  produces  erysipelas,  sometimes  phlegmons,  sometimes 
general  infections,  septicemias,  and  pyemias.  In  the  beginning  of 
bacteriological  study  facts  of  this  kind  seemed  inadmissible.  We 
were  so  used  to  our  nosographic  groupings  that  we  hesitated  to 
disturb  them  by  etiological  researches.  The  day  is  long  past,  how- 
ever, when  a  constant  relationship  between  disease  and  microbe  was 
obstinately  maintained.  It  is  now  admitted  by  all  that  one  and  the 
same  microbe  may  give  rise  to  most  varied  maladies.  In  order,  how- 
ever, to  justly  consider  an  animate  agent  as  the  cause  of  an  affection, 
it  is  necessary  to  isolate,  cultivate,  and  inoculate  it.  Here  other 
difficulties  are  encountered.  Certain  beings  visible  under  the  micro- 
scope do  not  develop  outside  the  organism  and  are  not  pathogenic 


58  INFECTIOUS  DISEASES. 

for  animals.  To  cite  the  best-known  example,  such  is  the  parasite 
of  malaria.  It  is  easy  to  understand,  therefore,  why  Laveran's 
discovery  was  not  readily  accepted.  Ten  years  of  ardent  discussion 
was  necessary  to  convince  the  opponents. 

Inoculation  of  the  pathogenic  agent — viz.,  the  reproduction  of  the 
observed  disease  in  animals — has  led  to  such  encouraging  results, 
and  its  methods  are  so  simple  that  it  is  resorted  to  on  every  hand. 

The  progress  of  experimental  pathology  has  been  most  wonderful, 
but  science  is  unfortunately  overrun  with  uncertain  and  erroneous 
data,  for  which  hasty  and  incomplete  contributions  are  responsible. 
Moreover,  owing  to  a  natural  tendency  of  the  human  mind,  experi- 
menters have  asked  of  the  laboratory  more  than  it  could  give.  Not 
contented  with  the  information  which  it  is  capable  of  furnishing  with 
regard  to  etiology,  they  wished  to  find  certain  and  accurate  indica- 
tions concerning  diagnosis,  prognosis,  and  treatment.  If,  in  certain 
instances,  experimentation  has  responded  to  all  that  was  asked  of 
it,  it  has  more  frequently  yielded  uncertain  and  misleading  results 
The  fact  is  that  there  is  no  constant  relation  between  the  virulence 
of  pathogenic  agents  for  man  and  their  action  upon  animals.  Experi- 
mentation demonstrates  this.  A  microbe  exhalted  for  one  species 
may  be  attenuated  for  another.  While  highly  virulent  for  man,  it 
may  be  harmless  for  laboratory  animals. 

Even  when  the  virulence  of  a  microbe  undergoes  no  variation  its 
effect  may  vary  greatly,  according  to  the  previous  state  of  the  in- 
vaded organism.  It  is  a  matter  of  frequent  occurrence  that  patients 
gravely  infected  transmit  a  mild  infection,  and  vice  versa.  The  his- 
tory of  variola  offers  numerous  illustrations  of  this  fact.  Likewise, 
two  individuals  contract  a  venereal  disease  on  contact  with  the  same 
woman — i.  e.,  under  conditions  as  identical  as  possible.  In  one  of 
the  cases,  however,  the  infection  is  benign;  in  the  other  it  pursues 
an  alarming  course. 

These  remarks  are  by  no  means  intended  to  diminish  the  impor- 
tance, but  to  indicate  the  difficulties  of  experimental  researches.  We 
shall  endeavor  to  lay  down  rules  which  should  guide  bacteriological 
experimentation . 

Role  of  Experimentation  in  the  Study  of  Infectious  Diseases. 
A  first  difficulty  is  the  choice  of  the  animal.  The  mouse,  the  guinea- 
pig,  and  the  rabbit  are  the  animals  most  frequently  experimented 
upon;  much  less  frequently  the  dog  and  the  monkey  are  employed. 
Larger  animals  are  difficult  to  manage  and  also  too  expensive.    What, 


GENERAL  CHARACTERS  OF  PATHOGENIC  B  ICTER1  I 

however,  complicates  the  problem]  is  the  fad  thai  some  di  i 
exclusively  human.  Syphilis  is  of  this  number.  In  such  ca  ee  the 
demonstration  of  the  pathogenic  agenl  become  a  matter  of  seriouc 
difficulty,  as  the  unquestionable  and  final  proof  i  lacking.  I  be  same 
remarks  are  applicable  to  other  infections  peculiar  to  man,  such  at 
mumps,  typhus  fever,  and  leprosy. 

The  impossibility  of  transmitting  certain  diseases  t<>  animal 
compelled  some  authors  to  operate  upon  man.     Long  before  the 
period  of  bacteriology  attempts  of  this  character  wen-  made,  and 
science  undoubtedly  benefited  by  the  inoculations  of  syphilitic  virus. 

Although  not  many  years  have  elapsed  since  thai  period,  a  higher 
and  more  just  conception  of  our  duty  toward  patients  intrusted  to 

our  care  has  caused  us  rightly  to  condemn  these  eriininal  attempts. 
At  the  present  day  nobody  would  venture  to  inoculate  the  virus  of 
syphilis,  variola,  or  cancer.  Should  the  subject  consenl  to  submit 
to  such  experiments,  it  would  be  our  duty  to  refuse  If,  however, 
an  investigator  believes  he  has  discovered  the  pathogenic  agent  of 
some  infection,  he  has  the  right  to  experiment  upon  himself. 

When  a  microbe  is  inoculated  into  an  animal,  three  results  are 
possible:  (1)  the  animal  may  be  endowed  with  natural  immunity  and 
resist  in  spite  of  all  efforts  of  the  experimenter;  (2)  it  may  contract 
a  disease  altogether  similar  to  that  from  which  the  microbe  under 
study  is  derived — in  which  case,  the  result  is  perfect  and  convincing ; 
(3)  finally,  it  may  present  morbid  symptoms  which  seem  to  have  no 
analogy  with  those  observed  in  man.  In  the  latter  instance  the 
experimenter  remains  in  doubt. 

The  last  result  may  be  illustrated  by  numerous  examples.  The 
pneumococcus,  for  instance,  produces  fibrinous  pneumonia  in  man. 
The  microbe  is  obtained  from  the  exudate,  cultivated,  and  then 
inoculated  into  a  rabbit  or  a  mouse,  which  dies  in  twenty-four  or 
forty-eight  hours  without  presenting  any  pulmonary  lesion.  It  has 
succumbed  to  a  genuine  septicemia. 

The  result  is  evidently  somewhat  discouraging.  It  must,  however, 
stimulate  the  experimenter  to  persist  in  his  researches,  for  by  chang- 
ing the  animals,  by  modifying  the  channel  of  introduction  of  the 
pathogenic  agent,  by  producing  various  concomitant  lesions,  or  by 
changing  the  culture  medium,  he  may  often  obtain  more  conclusive 
results.  Let  us,  therefore,  lay  down  the  principal  rules  of  experi- 
mentation. 

Inoculations  are  at  times  practised  with  virulent  material  taken 


60  INFECT  10 1 'S  D  IS  E.  I  N i'.s. 

directly  from  a  diseased  individual.  This  method  of  procedure  is 
now  abandoned  and  is  hardly  ever  resorted  to  since  the  introduction 
of  cultures.  It  may,  nevertheless,  be  of  service  in  those  instances 
in  which  the  pathogenic  agent  is  unknown.  In  hydrophobia,  for 
example,  direct  inoculations  only  are  made,  and  by  means  of  certain 
procedures  the  virus  is  modified  and  graduated  as  easily  as  if  it  had 
been  isolated  and  cultivated. 

In  some  cases,  even  when  it  is  possible  to  cultivate  the  microbe, 
it  may  be  preferable  to  make  inoculations  with  the  diseased  tissues, 
for,  while  the  passage  through  artificial  media  modifies  the  virulence, 
it  generally  weakens  it,  and  sometimes  imparts  to  it  particular  char- 
acters. Inoculations  in  series  are  equally  useful  for  strengthening  a 
virus  and  for  determining  the  virulence  of  a  microbe  in  the  organ- 
ism. The  last  consideration  guided  me  in  my  researches  on  avian 
tuberculosis.  With  Drs.  Cadiot  and  Gilbert,  the  author  inoculated 
directly  into  mammalia  tuberculous  products  derived  from  birds,  and, 
reciprocally,  tuberculous  products  of  mammalia  were  inoculated  into 
birds.  We  were  thus  able  to  determine  the  real  virulence  of  the 
bacillus.  The  results  proved  that  we  were  right  in  so  acting,  since 
the  employment  of  cultures  gives  rise  to  errors  of  interpretation. 

In  the  majority  of  cases  inoculations  are  made  with  pure  cultures. 
This  method  alone  furnishes  reliable  indications  as  to  the  nature  of 
the  pathogenic  agents.  It  alone  enables  us  to  differentiate  the  mi- 
crobes, to  interpret  their  biological  characters,  and  to  modify  their 
power  and  action  upon  the  organism.  The  variations,  however, 
which  occur  are  not  always  due  to  the  intervention  of  the  experi- 
menter. The  virulence  of  a  culture  is  sometimes  lessened  or  van- 
ishes for  some  unknown  reason.  This  inconvenience  has  recently 
been  remedied  by  modifying  the  culture  media  and  by  abandoning 
more  and  more  the  employment  of  bouillons.  Animal  fluids,  serum, 
ascitic  fluid,  pleuretic  effusion,  clefibrinated  blood  are  made  use  of 
instead.  These  are  sometimes  mixed  with  bouillon  or  agar-agar,  or 
the  cultures  are  prepared  within  the  living  organism  itself.  Small 
capsules  of  collodion  containing  the  microbe  are  introduced  into  the 
abdominal  cavity.  Diffusion  of  the  organic  fluids  readily  takes  place 
through  the  membrane,  which  protects  the  pathogenic  agent  against 
the  phagocytes. 

Even  under  these  conditions,  however,  the  cultures  do  not  always 
preserve  their  virulence  or  their  uniformity.  Just  as  with  the  higher 
organisms,  which,  when  placed  under  apparently  identical  conditions, 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA        v,\ 

are  always  dissimilar,  the  microbes  contained  in  8  medium  are  not 
all  endowed  \\  i  i  h  the  same  degree  of  vitality.  Among  t  he  individuals 
swarming  in  a  culture  capsule  some  are  more  active  or  more  pathogenic 
than  others.  11  is  very  difficult,  not  to  say  impossible,  to  obtain 
perfectly  uniform  cultures.  There  is,  however,  much  of  inti 
in  making  attempts  in  this  direction,  since  this  individual  vari- 
ability of  pathogenic  elements  is  I  lie  cause  of  many  eontradic 
results. 

Determinism  in  Bacteriology.  II  is  curious  to  note  how  little 
determinism  in  bacteriology  is  regarded.  The  reason  is,  perhaps, 
that  determinism  in  this  branch  of  research  presents  particular  diffi- 
culties. To  declare,  however,  that  a  bacterium  inoculated  into  sim- 
ilar animals  and  under  apparently  identical  conditions  produces 
different  effects  is  an  avowal  of  impotence.  That  such  diould  be 
the  case  with  regard  to  man  cannot  be  avoided.  We  must  submit, 
so  to  say,  to  the  caprices  of  clinical  phenomena.  We  are  victim-  of 
the  chances  and  accidents  of  observation.  In  experimental  | eth- 
ology, however,  we  must  endeavor  to  suppress  the  unforeseen  and  the 
inconstant.  We  must  seek  to  obtain  fixed  and  invariable  results. 
This  is,  of  course,  a  matter  of  great  difficulty,  for,  while  it  is  difficult 
to  determine  the  phenomena,  even  in  physiological  experiments,  the 
problem  is  far  more  complex  in  bacteriology.  Here  we  combine  two 
essentially  variable  factors.  The  animals,  in  spite  of  appearances, 
possess  individual  differences.  On  the  other  hand,  the  microbe,  as 
a  living  being,  possesses  no  immutable,  well-defined  properties  such 
as  are  peculiar  to  a  crystallized  chemical  poison.  The  result  is  that 
a  microbe  of  variable  action  is  introduced  into  an  animal  of  variable 
reactions.  The  causes  of  uncertainty  are  thus  added.  "While  it  is 
possible  to  interpret  certain  problems  and  to  determine  certain  phe- 
nomena, in  most  cases  this  means  to  displace  the  unknown.  For 
instance,  let  us  follow  the  passage  of  the  bacillus  anthracis  through 
the  placenta.  A  certain  number  of  pregnant  guinea-pigs  are  inocu- 
lated; at  the  necropsy  it  is  found  that  in  some  of  the  animals  the 
bacillus  has  invaded  the  foetus,  but  not  in  all.  Such  is  the  fact. 
Dr.  Malvoz  determined  this  by  showing  that  the  placenta  does  not 
permit  the  passage  of  organisms  except  when  it  is  altered.  If  it 
remains  intact,  it  acts  as  a  perfect  filter.  Consequently,  we  are  able 
to  state  precisely  that  the  bacillus  traverses  the  diseased  placenta, 
but  it  does  not  pass  through  the  intact  placenta.  It  is  evident, 
however,  that  the  problem  is  only  modified.     In  explaining  a  first 


62  IXFECTIO  US  DISEASES. 

point  a  new  one  is  introduced.  It  remains  to  determine  the  causes 
which  permit  or  prevent  localization  of  the  bacillus  in  the  placenta. 
When  we  become  acquainted  with  them  the  phenomenon  will  then 
be  elucidated. 

The  aim  of  the  experimenter  is,  therefore,  to  reproduce  in  animals 
constant  alterations  and  identical  modifications.  Next,  he  must 
vary  one  of  the  experimental  conditions  to  obtain  new  effects.  He 
will  then  be  master  of  the  phenomenon  and  be  in  a  position  to 
draw  conclusions  concerning  the  mechanism  of  infectious  occur- 
rences. 

Through  this  procedure  it  has  already  been  possible  to  solve  cer- 
tain questions  in  etiology  and  pathogenesis.  This  has  been  accom- 
plished by  modifying  the  local  or  general  resistance  of  the  animals 
by  various  means,  such  as  intoxication,  overwork,  fasting,  section  of 
nerves,  ligature  of  arteries,  traumatism  of  tissues,  etc.  Morbid  dis- 
positions are  created  thus,  and  the  results  obtained  lead  to  a  better 
understanding  of  the  mechanism  of  the  pathological  events. 

This  is  not  sufficient,  however.  A  more  profound  study  of  the 
lesions  is  required.  It  is  of  the  highest  interest  to  note  that  not 
every  part  of  a  diseased  organ  is  affected  in  the  same  measure.  Along 
with  diseased  cells  are  found  others  in  a  perfectly  healthy  condition. 
Thus,  after  particularization  of  the  species,  of  the  race,  and  of  the 
individual,  particularization  of  the  organs  and  tissues,  and,  pursuing 
the  analysis  still  further,  even  particularization  of  the  cells  has  been 
admitted.  This  fact,  which  is  not  without  interest  from  a  philo- 
sophical point  of  view,  is  the  outcome  of  pathological  studies.  Normal 
anatomy  and  physiology  could  not  lead  us  to  this  conclusion.  On 
section  of  a  normal  organ  or  tissue  all  the  cells  seem  alike.  It  is 
evident,  however,  that  if  they  were  all  alike  they  should  present  the 
same  alterations  under  the  influence  of  the  same  pathogenic  cause. 
It  is  difficult  to  explain  why  two  neighboring  cells  placed  apparently 
under  identical  conditions  are  differently  affected.  The  age  of  cells 
may  be  responsible.  These  elements,  according  to  the  universal  law 
governing  all  living  organisms,  succumb  and  are  renewed  unceas- 
ingly. Hence,  it  is  impossible  to  determine  whether  two  cells  close 
to  each  other  are  not  of  very  different  ages.  It  is,  then,  readily 
conceivable  that  their  resistance  should  vary  considerably  according 
to  their  ages.  It  must  also  vary  in  proportion  to  their  functional 
activity,  since  it  seems  to  be  certain  that  particular  parts  of  a  gland 
rest  while  other  parts  are  at  work.     If,  therefore,  for  any  of  the 


GENERAL  CHARACTERS  OF  PATHOGENIC  BACTERIA,       63 

reasons  above  indicated  certain  cells  are  more  affected  than  others, 
their  descendants  will  differ  from  otheri   Ln  their  morbid  aptitude) 

or  immunities. 
These  considerations  will  find  numerou    applications  in  the 

of  pathological  anatomy  and  physiology.     They  will  furni  h  u    with 
a  key  to  cellular  lesions. 


CHAPTER    III. 

ETIOLOGY  OF  INFECTIONS. 

Division  of  Infections,  According  to  Their  Origin,  into  Heteroinfections  and  Autoinfec- 
tions.  Transmission  by  Direct  Contact.  Transmission  through  Air,  Water,  and 
Soil.  Role  of  the  Invertebrates.  Transmission  through  Objects  and  Clothing. 
Disinfection  of  Apartments,  Effects,  Conveyances.  Transmission  by  Plants. 
Transmission  by  Food.  Autoinfections.  Distribution  of  Microbes  in  the  Normal 
Organism.  Importance  of  Auxiliary  Causes  in  the  Development  of  Infections. 
Influence  of  Regions,  Climates,  Seasons.  Influence  of  Race,  Age,  Sex.  Role  of 
Heredity  and  Innateness.  Action  of  External  Agents.  Role  of  Poisons.  Role  of 
Fasting  and  of  Fatigue.  Development  of  Epidemics;  Their  Modification  through 
Time  and  Space. 

Heterointoxications  and  Autointoxications. 

Infectious  diseases  may  be  clue  to  two  different  origins:  on  the 
one  hand,  the  pathogenic  germs  come  from  without,  and  their  intro- 
duction into  the  organism  is  the  evident  cause  of  the  morbid  process ; 
in  other  instances  they  are  already  present  within  the  organism  as 
simple  epiphytes  giving  rise  to  no  disturbance,  but  always  ready  to 
manifest  their  virulence  on  the  slightest  occasional  cause.  These 
divisions  are  indicated  by  the  terms  heteroinfection  and  autoinfection. 

The  recognition  of  autoinfections  is  of  recent  date  and  accounts 
for  the  numerous  facts  which  were  formerly  ascribed  to  morbid  spon- 
taneousness.  As  soon  as  the  microbes  resume  their  pathogenic  ac- 
tivity, however,  they  are  capable  of  invading  healthy  persons  and 
exerting  their  noxious  power:  the  disease,  born  spontaneously,  thus 
becomes  transmissible. 

A  disease  is  said  to  be  contagious  when  it  can  be  communicated, 
either  directly  or  indirectly,  by  a  diseased  individual  to  a  healthy 
one.  Although,  in  the  majority  of  cases  infecting  and  infected  indi- 
viduals belong  to  the  same  species,  this  is  not  always  the  case — man 
may  be  contaminated  by  animals. 

In  the  case  of  direct  transmission,  contagion  occurs  in  two  different 
ways:  either  by  contact  or  by  inoculation.  In  the  former  instance 
the  morbid  germs  derived  from  the  infected  subject  invade  the 
healthy  organism  through  unbroken  mucous  membranes,  generally 
through  the  respiratory  passages  or  the  alimentary  canal.     In  the 


ETIOLOGY  OF  INFECTIONS. 

latter  case  the  vims  is  deposited,  nol  upon  the  surface,  but  in  the 
interior  of  the  economy     i.  <•.,  in  a  wound  or  abra  ion.    'I  he  di 
is  then  said  bo  be  inoculated.     H  musl  be  noted,  however,  thai  i 
contagious  disease  is  inoculable,  but  thai  the  reverse  i    uol  true. 

Recent  epidemiological  researches  tend  considerably  to  limit  the 
r61e  played  by  air.  They  show  that  transportation  i  .  a  a  rule, 
effected  l>y  persons  imd  objects.  Of  the  latter  the  besl  known  are 
the  utensils  employed  at  meals,  such  as  forks,  spoon-,  and  gla 
those  used  for  the  toilet,  such  as  brushes,  combs,  and  sponges.  Cloth- 
ing, bedding,  books,  letters,  and  coins  find  paper  money  mufll  also 
be  mentioned.  Finally,  in  many  cases  in  which  propagation  by  air 
seemed  to  be  demonstrated,  if  is  now  recognized  that,  in  reality, 
transmission  occurs  through  the  agency  of  certain  insects  which  in- 
gest the  microbes  and  then  deposit  them  beneath  the  skin  by  true 
inoculation.     Such  is  notably  the  case  in  malaria. 

When  ejected  from  the  diseased  organism,  certain  germs  rapidly 
-die;  others  often  survive  for  a  long  time  in  water  and  soil,  upon 
floors,  walls,  etc.  We  must,  therefore,  study  these  diverse  origins 
-of  infections  in  their  order. 

Transmission  of  Infections  by  Contact.  Let  us  first  consider 
the  simplest  case — i.  e.,  transmission  by  immediate  contact  of  healthy 
with  diseased  individuals.  Here  is  an  example  of  genuine  inoculation 
which  sometimes  requires  a  previous  erosion  of  tissues.  At  other 
times  inoculation  is  effected  through  the  intact  epithelia,  as  occurs 
in  venereal  diseases:  gonorrhea,  soft  chancre,  and  syphilis.  Such 
immediate  contact  is  not,  of  course,  indispensable,  since  the  virus 
may  be  deposited  upon  objects  which  serve  for  its  transmission. 
The  characteristic  feature  of  this  group  is  the  fact  that  the  patho- 
genic agents  manifest  little  if  any  tendency  to  diffusion.  They  are 
not  propagated  by  air  or  water  and  they  do  not  vegetate  outside  the 
organism.  It  has  been  said  that  the  gonorrheal  virus  embodied  in 
pus  particles  may  be  spread  by  air,  and  in  this  maimer  epidemics 
of  purulent  ophthalmia  invading  a  hospital  ward  are  sometimes 
explained.  It  must  be  remembered,  however,  that,  in  most  cases, 
minute  inquiry  demonstrates  that  propagation  is  due  to  immediate 
contact.  The  same  is  true  of  vulvovaginitis  in  children :  the  microbe 
is  conveyed  by  the  mother's  contaminated  hands,  toilet  articles,  and 
particularly  by  sponges.  Anthrax,  glanders,  and  at  times  tubercu- 
losis and  actinomycosis  may  also  be  directly  transmitted  by  acci- 
dental  inoculation.      The    same    should   be    true  of   hydrophobia. 


Q  Q  INFE  OTIOUS  DISEA  SES. 

although,  in  this  regard,  there  is  as  yet  no  convincing  observation. 
Bites  by  hydrophobic  individuals  have  thus  far  never  given  rise  to 
the  disease. 

In  a  second  group  may  be  classed  those  infectious  germs  which 
are  capable  of  transmission  to  a  distance  through  the  agency  of 
squama1,  urine,  expectoration,  etc.  The  cutaneous  squama?  are 
often  considered  the  agents  of  transmission  of  the  eruptive  fevers 
and  erysipelas.  For  the  latter  disease,  however,  the  mechanism  of 
transmission  is  scarcely  acceptable,  since  bacteriological  researches 
demonstrate  that  the  products  of  desquamation  contain  no  strepto- 
cocci. 

The  transmissibility  of  eruptive  fevers  varies  according  to  the 
infection  considered. 

The  germ  of  measles  is  contained  in  the  oculonasal  secretions  and 
saliva,  as  was  demonstrated  by  the  successful  inoculations  made  by 
Monro  and  Looke  in  the  eighteenth  century,  and  by  Mayo  in  1860. 
In  accordance  with  these  experiments,  observation  teaches  us  that 
measles  is  contagious  before  the  stage  of  eruption,  and  soon  ceases 
to  be  so,  since  five  or  six  days  after  the  appearance  of  the  exanthem 
the  germ  seems  to  be  destroyed.  In  very  rare  exceptions  convales- 
cents from  measles  have  been  known  to  infect  healthy  persons  fifteen 
and  even  thirty  days  after  the  beginning  of  the  disease. 

The  squamae  are  generally  believed  to  be  the  media  for  the  trans- 
mission of  the  germs  of  scarlatina.  According  to  recent  researches 
by  Dr.  Lemoine,  however,  the  morbid  germs  are  found  in  the  secre- 
tions of  the  throat,  and  the  disease  may  thus  be  transmitted  before 
the  appearance  of  the  eruption.  By  questioning  scarlatinal  patients 
I  have  found  in  several  cases  that  the  typical  disease  had  developed 
in  consequence  of  contact  with  an  individual  suffering  merely  from 
a  sore  throat. 

As  in  measles,  the  germ  of  scarlatina  is  found  in  the  throat  and 
not  in  the  squama?.  The  latter  may  become  the  media  of  transmis- 
sion in  so  far  as  they  are  apt  to  be  contaminated  by  the  saliva  of 
the  patient.  It  is  also  to  be  remembered  that  the  virus  of  scarlatina 
is  more  persistent  than  that  of  measles.  The  period  of  forty  days, 
fixed  by  the  Council  of  Hygiene  (of  Paris),  is  generally  sufficient, 
though  contamination  has  exceptionally  taken  place  after  the  expi- 
ration of  this  time.  Unlike  the  scarlatina  germ,  that  of  measles 
possesses  but  slight  viability  and  diffusibility.  Two  or  three  hours 
outside  of  the  diseased  organism  is  sufficient  to  destroy  the  virus. 


ETIOLOGY  OF  INFECTIONS.  <;7 

Epidemiology  of  Smallpox.  The  study  of  smallpox  strikingly 
illustrates  the  mode  of  propagation  of  epidemics  of  thi   di  ei 

The  microbe  of  smallpox,  by  its  greal  resistance,  seem    to  clo 
resemble  that  of  scarlatina,  bul  it  is  far  less  diffusible.     I' 
mission  through  air  has  not  been  demonstrated.     In  man} 
which  this  mode  of  propagation  was  assumed  inquiry  established 
that  a  patient  or  some  attendant  bad,  in  violation  of  instructions, 
trespassed  the  boundaries  of  isolation,  or  that  disinfection  ol  con- 
taminated objects  had  not  been  thorough. 

During  the  epidemic  which  raged  in  1900  we  received  928  patient* 
in  the  Hospital  d'Aubcrvilliers.  Of  this  number,  246  had  been  con- 
taminated directly  by  contact  with  individuals  suffering  from  variola. 
We  have  established  a  rule  that  a  smallpox  patient  must  remain  in 
the  hospital  for  at  least  forty  days.  Those  who  need  a  certificate 
for  resuming  their  work  respect  the  rule,  but  others,  under  various 
pretences,  leave  the  hospital  too  soon  and  spread  the  disease.  The 
study  of  the  epidemic  of  1900  further  shows  that  the  poorer  sec- 
tions of  Paris  suffered  most,  since  the  rules  of  hygiene  are  not  well 
observed  by  the  inhabitants  of  these  quarters.  When  there  is  a 
patient  in  a  workman's  family  the  neighbors  often  come  to  nurse  the 
sick,  and  then  return  home  or  to  work  without  taking  any  precau- 
tions. In  one  of  my  observations  the  janitress  nursed  a  poor  indi- 
vidual attacked  by  smallpox,  and  the  devotion  of  this  brave  woman 
resulted  in  the  transmission  of  the  malady  to  the  majority  of  the 
tenants. 

The  mildest  cases  are  particularly  dangerous  for  the  public.  An 
individual  is  seized  with  malaise,  muscular  pain,  fever,  and  at  times 
with  rachialgia.  He  stays  at  home  for  three  or  four  days.  An 
eruption  then  makes  its  appearance:  a  dozen  large  papules  resem- 
bling acne  appear  upon  his  face.  At  this  time  the  patient  feels  well, 
and  resumes  his  occupation.  Not  having  consulted  a  physician,  he 
is  ignorant  of  the  nature  of  the  disease.  It  must  also  be  remembered 
that  many  physicians  are  unable  to  diagnose  variola  since  epidemics 
have  become  rare.  Nevertheless,  the  failure  of  a  physician  to  recog- 
nize smallpox  has  often  been  the  cause  of  its  propagation. 

Epidemics  in  General.  It  seems  that  the  study  of  conditions 
governing  the  development  of  epidemics  in  general  tends  more  and 
more  to  reduce  the  role  of  transmission  at  a  distance  and  to  empha- 
size the  importance  of  direct  contamination.  The  latter  mode  is 
most  often  responsible  for  the  infection  of  wounds.    Though  trans- 


68  IXFECTIO  US  DISEASES. 

mission  by  air  is  possible,  propagation  is,  in  the  majority  of  cases, 
effected  through  insufficiently  cleansed  instruments  and  hands. 

Some  twenty  years  ago,  when  infection  of  wounds  was  still  fre- 
quent, I  had  the  opportunity  to  observe  an  epidemic  of  erysipelas 
in  a  surgical  ward.  The  first  case  was  seen  one  morning.  The 
following  day  a  second  case  occurred,  and  others  appeared  on  sub- 
sequent days.  Transmission  by  air  and  the  infection  of  the  ward 
was  assumed.  On  studying  the  course  of  the  epidemic,  however,  it 
was  noticed  that  only  those  patients  had  been  attacked  at  whose 
bedsides  the  attendant  surgeon  and  his  assistants  had  stopped.  The 
latter  had  received  the  germ  of  erysipelas  from  the  first  patient  and 
conveyed  it  to  the  others.  Those  patients  who  had  not  been  visited 
remained  exempt.  Here,  then,  is  a  series  of  facts  contrary  to  the 
theory  of  the  distribution  of  contagium  through  the  air. 

Infection  may  also  be  contracted  by  contact  with  diseased  animals. 
In  certain  instances  the  virus  is  deposited  directly  in  a  wound;  at 
other  times  by  means  of  a  bite,  as  in  the  case  of  hydrophobia ;  or  by 
accident  in  handling  diseased  animals  or  cadavers.  It  has  been 
asserted  that  scarlet  fever  is  an  infection  of  bovine  origin  and  that 
it  may  be  propagated  by  milk  (Klein).  Some  authorities  believe 
that  all  the  eruptive  fevers  are  of  animal  origin.  Finally,  an  infec- 
tion of  parrots,  which  has  recently  been  studied  and  is  due  to  a 
bacillus  related  to  the  colon  bacillus,  is  highly  virulent  for  man. 
This  infection  is  known  as  psittacosis. 

Transmission  of  Tuberculosis  by  Contact.  Of  all  infections 
tuberculosis  is  incontestably  the  most  readily  transmitted  among 
different  beings.  Direct  contamination  of  the  healthy  man  by  dis- 
eased animals  is  no  longer  a  matter  of  doubt  since  the  unity  of 
tuberculosis  in  all  animals  has  been  admitted.  While  there  are  sev- 
eral varieties  of  Koch's  bacillus  the  differences  separating  them  are 
not  of  sufficient  dignity  to  constitute  specific  characters.  From  a 
scientific  standpoint,  it  is  generally  admitted  that  the  digestive 
organs  may  be  infected  by  ingestion  of  the  flesh  or  milk  of  tuber- 
culous animals.  The  frequency  of  such  cases  has  not,  however,  been 
established. 

Direct  inoculation  of  tuberculosis  seldom  takes  place.  Several 
cases  have  been  published  concerning  Hebrew  children  who  became 
infected  as  a  result  of  circumcision  practised  according  to  the  rite, 
requiring  the  operator  to  arrest  hemorrhage  by  oral  suction.  Modern 
researches  have  demonstrated  the  anatomical  tubercle  to  be  a  gen- 


ETIOLOQ  V  OF  INFECTIONS.  69 

uine  bacillary  tubercle.  II.  is  well  to  remember  thai  direct  inoculation 
may  occur  from  bovidse  to  man.  The  observation  reported  by 
Pfeiffer  is  a  most  remarkable  one.  Moser,  a  veterinarian  of  Weimar, 
wounded  himself  in  making  a  necropsy  upon  a  tuberculous  cow. 
months  later  a  cutaneous  tuberculosis  developed  al  the  point  of  the 
cicatrix,  lie  died  from  pulmonary  tuberculosis  two  and  a  balf 
after  infliction  of  Hie  wound.  Tscherning  and  Ponfick  love  cited 
similar  cases.  The  researches  of  Verneuil  and  of  Femel  have  fully 
demonstrated  the  transmissibility  of  tuberculosis  by  sexual  inter- 
course. Cornil  and  Dobroklonsky  produced  tuberculosis  in  guinea- 
pigs  by  injecting  bacilli  into  (heir  vaginal  canals. 

Transmission  of  Infections  through  the  Air.  Alter  the  con- 
tagious elements  have  passed  out  of  the  diseased  body  they  may 
be  dispersed  by  the  air,  transported  by  water,  and  reside  in  the  soil, 
awaiting  an  occasion  to  invade  a  new  organism. 

Transmission  by  the  air,  although  not  of  such  frequent  occurrence 
as  was  formerly  believed,  is,  nevertheless,  undeniable.  The  air  con- 
tains a  great  number  of  microbes,  as  is  shown  by  the  following  figures 
obtained  by  Miquel.  These  figures  demonstrate  the  considerable 
variations  observed  in  different  localities: 

On  sea,  at  100  kilometres  from  the  coast      .           .           .  0.6 

Altitude  of  2000  metres 3.0 

Summit  of  the  Pantheon 200.0 

Observatory  of  Montsouris            ......  480.0 

Rue  de  Rivoli .  3,480.0 

New  houses          .........  4,500.0 

Sewers  of  Paris 6,000.0 

Old  houses 36.000.0 

Hotel  Dieu .  40,000.0 

Hopital  do  la  Pitio 79.000.0 

In  perusing  this  table  it  is  surprising  to  note  that  the  air  of  sewers 
does  not  contain  many  more  microbes  than  that  of  a  new  house,  anil 
contains  one-sixth  as  many  as  the  air  of  an  old  house.  The  reason 
for  this  is  that  the  innumerable  bacteria  residing  in  the  water  cannot 
enter  the  air.  This  has  been  demonstrated  by  experiments:  a  cur- 
rent of  air  passing  over  a  contaminated  liquid  does  not  take  up 
microbes. 

The  various  figures  above  given  have  but  a  relative  value.  Con- 
siderable variations  occur  each  day  in  the  same  locality.  The  number 
of  microbes  increases  when  a  violent  wind  raises  the  dust,  and  dimin- 
ishes after  a  rain  which  sweeps  them  down  toward  the  soil.  During 
the  hot  season  the  microbes  increase.     According  to  Dr.  Miquel.  the 


70  INFECTIOUS  DISEASES. 

average  number  of  bacteria  contained  in  the  air  of  Monsouris  is 
170  in  winter,  295  in  spring,  345  in  summer,  and  195  in  autumn. 
The  highest  figures  were  found  in  July  and  the  lowest  in  De- 
cember. 

It  has  generally  been  thought  sufficient  to  count  the  number  of 
microbes  in  the  air  without  ascertaining  the  proportion  of  pathogenic 
agents.  However,  Ullmann  detected  staphylococci  in  the  air  of  a 
surgical  ward,  and  Eiselsperg  and  Emmerich  found  streptococci.  The 
latter  microbe  seems  to  be  quite  widely  distributed  in  the  atmos- 
phere, or  at  least  a  variety  of  it  is  quite  frequently  met  with  in 
decaying  substances.  It  has  also  been  demonstrated  that  air  may 
convey  the  contagium  of  diphtheria,  typhoid  fever,  and  the  eruptive 
fevers.  As  already  stated,  however,  this  is  seldom  the  case.  Even 
influenza  does  not  attack  those  persons  who  have  not  been  in  contact 
with  those  suffering  from  the  malady,  and,  although  its  propagation 
is  often  rapid,  it  is  not  any  more  so  than  our  means  of  communica- 
tion. Epidemics  are  engendered  not  by  the  air  but  by  the  agency 
of  individuals. 

Transmission  of  Tuberculosis  by  Inhalation.  From  a  bac- 
teriological standpoint,  the  air  expired  from  the  lungs  of  a  tuber- 
culous patient  is  pure,  since  it  contains  no  tubercle  bacilli  or  any 
other  microbe.  The  real  danger  resides  in  the  expectoration.  Pro- 
tected by  the  organic  particles  in  which  it  is  incorporated,  the  ba- 
cillus retains  its  vitality  in  the  dried  sputa  for  a  long  period  and  is 
distributed  far  and  wide.  The  protected  bacillus  is  more  dangerous 
than  the  free  microbes,  because  the  animal  and  vegetable  detritus 
containing  it  act  as  foreign  bodies  and  give  rise  to  inflammatory 
reactions  which  favor  "  tuberculization." 

Numerous  experiments  have  proved  that  inhalation  is  a  far  more 
certain  mode  of  contagion  than  ingestion.  In  this  connection,  Tap- 
peiner's  researches  upon  dogs  leave  no  room  for  doubt.1 

It  is  not  correct,  however,  to  say  that  the  bacilli  are  carried  by 
the  dried  sputa  alone.  The  researches  of  Fluegge  and  his  disciples, 
which  have  been  confirmed  by  Moeller,  have  established  that  a  con- 
sumptive, when  speaking  or  coughing,  projects  about  him  a  sort  of 
microscopic  spray  of  mucus  and  saliva  charged  with  tubercle  bacilli. 
The  persons  surrounding  him  are  thus  exposed  to  the  danger  of  con- 
tracting the  disease. 

1  Tappeiner.  TJeber  eine  neue  Methode  Tuberculose  zu  erzeugen.  Vircliow's  Arch., 
1878.     Neue  exp.  Beitrage  zur  Inhalationtuberculose.     Ibid.,  1880. 


ETIOLOGY  OF  INFECTIONS.  71 

Conveyance  of  Infection  by  Water.  The  transmi  ion  of  infec- 
tious diseases  through  the  agency  of  water  is  far  more  frequenl 

than  by  means  of  the  air.  This  fact  was  known  to  the  anciente,  who 
used  aromatic  infusions  as  beverages,  thus  employing  a  very  rational 
method  of  sterilization.  In  passing  through  the  soil,  water  free 
itself  of  microbes.  Spring  water,  therefore,  when  taken  a!  its  ource, 
is  often  absolutely  sterile.  For  this  to  occur,  however,  water  must 
percolate  through  porous  st  rata,  When  \\  filters  through  calcareous 
strata,  making  its  own  little  channel,  it  retains  its  microbes.  Such 
are  the  waters  of  Avre  and  Vanne,  which  supply  Paris.1  A-  3oon  as 
it  enters  upon  its  course,  spring  water  begins  to  acquire  bacteria. 
Even  hot  mineral  spring  water  contains  bacteria. 

It  is  readily  understood  that  bacteria  become  more  numerous  when 
a  water-course  traverses  a  city.  We  must  remember,  however,  thai 
running  water  purifies  itself  quite  rapidly.  The  following  figures 
are  convincing:  The  water  of  the  Izar  before  its  passage  through 
Munich  contained  305  bacteria  per  cubic  centimetre.  At  its  exit 
from  the  city,  after  having  received  the  contents  of  the  sewers,  it 
contained  12,600  per  cubic  centimetre.  Thirteen  kilometres  further 
down  the  figure  is  reduced  to  2400  per  cubic  centimetre.  This 
natural  depuration  is  likewise  effected  in  reservoirs.  The  water  of 
the  Thames,  for  instance,  contains  1437  bacteria  per  cubic  centi- 
metre. It  contains  only  318  per  cubic  centimetre  after  its  passage 
into  a  first  reservoir,  and  177  per  cubic  centimetre  at  its  exit  from 
a  second.  As  already  stated,  the  action  of  the  sun  is  more  powerful. 
Fewer  microbes  are  found  at  8  p.m.  than  early  in  the  morning.  The 
number  may  thus  fall  from  520  to  5  per  cubic  centimetre. 

Epidemiological  and  bacteriological  researches  have  led  to  prophy- 
lactic principles  of  importance.  The  water  origin  of  typhoid  fever, 
cholera,  and  dysentery  seems  to  be  definitely  established.  In  regard 
to  typhoid  fever,  the  history  of  epidemics  is  at  least  as  important  as 
bacteriological  researches,  since  it  is  difficult  to  separate  and  differ- 
entiate the  colon  bacillus  from  the  typhoid  bacillus,  when  these  two 
microbes  are  present  in  the  same  fluid.  The  errors  that  have  been 
made  in  this  respect,  however,  have  led  to  wise  hygienic  precautions. 
At  the  same  time  a  more  minute  study  of  pathogenesis  has  developed 
new  ideas  concerning  the  origin  and  spread  of  infections.  It  has  been 
questioned  whether  the  role  of  water  was  not  a  complex  one ;  whether. 

1  Thoinot.  Lcs  sources  tie  la  craie  et  la  fievre  typhoidc.  Presse  medicate.  Feb.  14. 
1900. 


72  I -XFECTIO  US  DISEASES. 

in  addition  to  the  possible  presence  of  pathogenic  agents,  it  was 
necessary  to  weigh  the  action  of  saprophytes  capable  of  favoring 
their  development.  Authorities  are  now  inclined  to  admit  this 
theory  with  regard  to  cholera  and  typhoid  fever.  It  accounts  for 
those  cases  in  which  the  disease  attacked  persons  who  had  drunk 
from  a  reservoir  polluted  by  percolations  from  cesspools.  Typhoid 
fever  has  developed  even  when  the  matters  were  derived  from  indi- 
viduals free  from  this  disease  or  who  had  suffered  from  it  a  year 
before.  At  the  end  of  so  long  a  period  the  bacillus  was  certainly 
destroyed.  In  fact,  according  to  the  researches  of  Karlinski,  it  is 
known  that  the  microbe  does  not  survive  in  fecal  matters  for  more 
than  three  months.  This  fact,  which  is  often  cited  in  support  of  the 
specific  origin  of  the  disease,  seems  rather  to  lead  to  a  contrary 
conclusion. 

Whatever  mode  is  responsible,  it  is  certain  that  water  causes  the 
majority  of  epidemics  and  explains  their  recrudescence  in  regions 
where  the  disease  is  endemic.  In  this  connection  nothing  is  more 
instructive  than  the  researches  of  Drs.  Brouardel,  Chantemesse,  and 
Widal.  These  authors  showed  that,  in  Paris,  in  1885,  1886,  and 
1887,  typhoid  fever  suddenly  increased  twelve  or  fifteen  days  after 
the  population  was  supplied  with  river  water,  and  disappeared  as 
soon  as  spring  water  was  again  furnished. 

The  survival  of  germs  in  water  has  been  studied  by  various  authori- 
ties. Straus,  Dubary,  and  Hochstetter  have  produced  figures  in 
evidence  of  the  effects  exerted  by  diverse  conditions,  such  as  the 
composition  of  the  water,  presence  of  other  microbes,  dissolved  sub- 
stances, and  the  action  of  carbonic  acid,  as,  for  example,  in  seltzer 
water.  In  this  connection  it  should  be  remarked  that  carbonic  acid 
under  pressure  confers  no  germicidal  property  upon  seltzer  water. 
Although  the  non-sporulating  anthrax  bacillus  dies  in  it  within  an 
hour,  the  typhoid  bacillus  resists  for  from  five  clays  to  twelve  days, 
that  is,  about  the  same  as  in  ordinary  water. 

The  conclusion  is  that  water  furnished  for  drinking  purposes 
always  contains  microbes. 

Transmission  of  Infections  by  the  Soil.  The  soil  receives  as 
many  microbes  as  does  water.  These  sink  deep  into  the  soil,  but 
no  further  than  three  and  one-half  to  four  yards  below  the  surface. 
At  this  depth  the  soil  becomes  sterile.  The  maximum  is  found  at 
twenty  inches  (C.  Fraenkel).  Those  remaining  upon  the  surface  are 
rapidly  destroyed  by  the   sun's  rays.     However,  a  little  soil  or  dust 


ETIOLOGY  OF  INFECTIONS. 

taken  at  the  surface  of  I, he  road  almost  constanl  ly   Ikw     ome  patho- 
genic, agents:  pyogenic  cocci,  the  bacillu    of  gaseou    gangri 
tetanus,  and  in  certain  localities  the  bacillus  anthracis,     Clinical 
studies  supplementing  the  data  of    bacteriological    research  have 

established  the  telluric  origin  of  the  agents  of  <l.\  cholera, 

typhoid  fever,  tuberculosis,  and  icterus  gravis.   These  various  ag 

as  above  stated,  are  found  in  and  nol   upon  the  surface  of  the  -oil. 
They  are   brought   to   the   surface   on    various   occn-ions   when 

instance,  the  soil  or  streets  are  dug  or  torn  up  for  diverse  pur} 
Such  work  is  too  often  followed  by  the  outbreak  of  epidemii 
typhoid  fever,  diarrhea,  or  icterus  gravis. 

Role  of  the  Invertebrates  in  the  Transmission  of  Infections. 
It  has  long  been  known  that  certain  pastures  were  particularly  dan- 
gerous as  centres  of  anthrax  infection.  In  Beauce  such  pastures 
were  called  "cursed  fields."  At  times  the  focus  was  confined  to  a 
farm  or  a  stable.  Pasteur  undertook  the  study  of  this  mysterious 
question  and  discovered  anthrax  spores  in  the  infecting  soil  in  the 
neighborhood  where  anthrax  animals  had  been  buried  several  years 
before.  Pasteur  asserted  that  earthworms  ingested  the  spores  with 
the  contaminated  soil  and,  coming  to  the  surface,  deposited  them 
with  their  excreta.  Koch  vigorously  opposed  Pasteur's  theory.  He 
argued  that  the  soil  is  too  cold  to  permit  the  vegetation  and  particu- 
larly the  sporulation  of  anthrax.  The  soil,  however,  seems  to  be  a 
good  culture  medium.  Soyka1  proved  by  experiment  that  the  intro- 
duction of  particles  of  quartz  into  liquids  in  which  bacteria  are  culti- 
vated markedly  favors  sporulation.  It  is  further  to  be  remarked 
that  the  temperature  of  the  soil  is  higher  around  buried  cadavers 
because  of  the  heat  generated  by  putrefaction. 

Earthworms  are  not  the  only  animals  capable  of  conveying  anthrax. 
The  highly  interesting  experiments  of  Karlinskr  demonstrate  that 
snails  may  play  the  same  role.  Living  spores  were  found  in  their 
intestines  eleven  days  after  ingestion  of  food  containing  anthrax 
bacilli.  Insects,  particularly  flies,  are  often  the  agents  of  microbic 
transmission.  At  times  the3f  simply  transport  the  germs  from  one 
point  to  another.  At  other  times  they  inoculate  them  into  healthy 
individuals.  The  typhoid  bacillus  passes  through  the  intestine  of 
the  fly  without  perishing.     Flies  may  also  disseminate  the  tubercle 

1  Soyka.     Bodenfeuchtigkeit  uud  Milzbrandbaeillus.     Fortschritte  d.  Med..  lxv 

2  Karlinski.  Zur  Kenntniss  der  Verbreitungswege  des  Milzbraudes.  Centralbl.  f. 
Bakt.,  1889,  Bd.  v. 


74  INFECTIOUS  DISEASES. 

bacillus,  as  has  been  proved  by  Spillmann,  Haushalter,  Hoffmann,  and 
Moeller.  As,  however,  the  common  fly  is  incapable  of  biting  man,  it 
simply  diffuses  the  virus. 

The  role  of  mosquitoes  is  much  more  important.  As  early  as  1848 
Nott  believed  they  conveyed  yellow  fever.  In  1898  Grassi  estab- 
lished the  law  of  coincidence  of  malaria  and  certain  mosquitoes — 
the  Anopheles  and  especially  Anopheles  claviger.  The  bite  of  Culex 
pipiens  is  less  dangerous,  though  not  completely  harmless  (Laveran, 
Bignami,  Bastianelli,  etc.).  It  is  also  known  that  the  African 
cattle  disease  caused  by  the  tsetse  fly  is  not  due  to  venom,  as  was 
once  supposed,  but  to  inoculation  of  a  parasite,  trypanosoma  Evansi. 
Bed-bugs  may  transport  tuberculosis  (Dewevre)  and  recurrent  fever 
(Tiktine),  while  spirilla  die  inside  these  animals  in  forty -eight  hours. 
The  majority  of  other  microbes  perish  very  rapidly,  so  that,  according 
to  Nuttal's  experiments,  bed-bugs  do  not  seem  to  be  capable  of 
propagating  anthrax  or  bubonic  plague.  Ogata  has  shown  that  fleas 
found  upon  rats  suffering  from  plague  often  contain  the  pathogenic 
bacillus.  The  flea  of  the  rat  is  not,  however,  identical  with  that  of 
man,  and  seems  to  be  incapable  of  biting  him. 

All  these  extremely  interesting  facts  tend  further  to  reduce  the 
role  of  the  air  and  to  establish  the  conclusion  that  infections  are  most 
frequently  propagated  by  contact. 

Role  of  Objects,  Clothing,  and  Draperies.  As  early  as  1868 
Villemin  rightly  declared  that  "  residences  are  foci  of  infection  for 
man,  and  should  be  disinfected  as  is  a  stable  contaminated  by  glan- 
ders." The  floors,  rugs,  draperies,  all  furniture,  and  particularly 
clothing,  may  receive  and  carry  infectious  germs.  Numerous  in- 
stances demonstrate  that  clothing  may  cause  the  reappearance  of  an 
infection  several  years  after  exposure.  Such,  for  example,  was  the 
case  with  the  clothing  of  a  child,  the  victim  of  diphtheria,  which  had 
been  placed  in  a  drawer  and  thus  protected  against  the  action  of 
light.  A  year  or  two  later,  when  taken  out,  they  gave  rise  to  fresh 
cases  of  diphtheria.  Hence  the  necessity  for  vigorous  disinfection 
of  apartments,  bedding,  clothing,  and  vehicles  of  transportation 
which  have  served  for  the  conveyance  of  a  sufferer  from  some  infec- 
tious disease. 

Role  of  Plants.  Infections  may  also  be  due  to  contamination 
by  plants  carrying  pathogenic  agents.  This  is  particularly  the  case 
in  aspergillosis  and  actinomycosis.  The  former  disease  attacks  those 
who  rear  pigeons,  not  because  the  birds  are  diseased,  but  because 


ETIOLOQ  )'  OF  INFECTIO  75 

fche  individuals  who  feed  them  pul   into  their  own  mouths  grain 
contaminated  with  aspergillus  fumigatus.     Actinomyco 
rarely  contracted  from  men  or  animals.     Man  and  the  bovidae  are 
almost  always  infected  through  the  agency  of  contaminated  eai 
corn  or  grain  when  the  latter  are  chewed  or  (lie  subjects  are  pri 
by  thoin. 

Role  of  Aliments.     Infections  may  be  transmitted  through  inj 
tion  of  meat,  viscera,  and  milk  of  diseased  animals. 

Some  authorities  claim  that  the  flesh  of  animals  suffering  from 
anthrax  may  be  consumed  with  impunity.  According  to  Johne,  the 
meat  contains  no  spores.  This  assertion  is  contradicted  by  the 
experiments  of  Schmidt-Muhlheim.  This  scientisl  showed  that  Johne 
had  examined  only  the  interior  of  the  meat,  and  that  sporulation  i- 
possible  upon  the  surface  in  contact  with  air.  Such  flesh  should  be 
proscribed,  if  for  no  other  reason  than  to  avoid  the  danger  to  which 
those  who  handle  it  are  exposed.  In  the  German  statistics  for  Is ^7 
it  is  found  that  anthrax  developed  twelve  times  through  the  use 
of  contaminated  meat.  According  to  Puech,  salting  may  destroy 
virulence.  The  experiments  of  Foster  and  Freytag  contradict  this 
conclusion.  By  growing  anthrax  in  agar-agar  containing  an  excess 
of  salt  these  authors  discovered  that,  while  the  bacilli  died  in  twenty- 
four  hours,  the  spores  survived  for  several  months.  It  must  be 
remembered  that  the  milk  of  animals  infected  with  anthrax  may  con- 
tain virulent  bacteria,  as  has  been  established  by  the  researches  of 
Chambrelent,  Moussous,  and  Karlinski. 

As  regards  the  flesh  of  tuberculous  animals,  the  Congress  of  lsss 
demanded  the  total  proscription  of  such  meat.  It  is  as  yet  difficult 
to  express  a  final  opinion  in  this  respect.  A  certain  number  of 
tradictory  experiments  have  been  reported.  Cooking  and  the  action 
of  the  gastric  juice  do  not  suffice  to  destroy  the  tubercle  bacillus. 
Finally,  although  the  microbe  is  not  present  in  the  muscles  it  is 
with  in  the  glands,  and  this,  perhaps,  is  a  sufficient  reason  for  pro- 
hibiting the  consumption  of  such  meat. 

Role  of  Milk.  Since  Gerlach  recognized  that  the  milk  of  dist ,  - 
cows  may  transmit  tuberculosis,  numerous  experiments  have  con- 
firmed his  view  and  demonstrated  the  role  of  this  fluid  in  the  etiology 
of  abdominal  tuberculosis  in  children  ( Klebs,  Orth,  Cohnheim).  From 
a  hygienic  standpoint,  Gerhardt  published  an  extremely  interesting 
work  upon  this  subject.  Milk  purchased  in  ten  different  places  in 
Munich  did  not  transmit  tuberculosis.     On  the  other  hand,  the  milk 


76  IXFECTIOCS  DISEASI-JS. 

of  consumptive  cows  always  proved  virulent.  When  this  milk  was 
diluted  with  forty  to  one-hundred  volumes  of  non-infected  milk, 
however,  it  was  rendered  harmless.  This  is  just  what  occurs  in 
dairies.  The  researches  of  Bang  demonstrated  the  presence  of  vir- 
ulent bacilli  in  butter.  Heating  of  milk  is,  therefore,  absolutely 
necessary.  In  this  connection  it  should  be  remembered  that  a  tem- 
perature of  65°  C.  (149°  F.),  and  even  70°  C.  (158°  F.),  is  not  always- 
sufficient  to  destroy  pathogenic  germs.  Ingestion  of  milk  thus 
treated  has  resulted  in  the  transmission  of  the  disease  to  swine, 
while  rabbits,  which  are  less  sensitive  to  this  mode  of  infection, 
usually  resisted  infection  (Bang). 

Since  the  milk  of  tuberculous  cows  so  often  proves  to  be  virulent, 
we  may  justly  assume  that  the  milk  of  consumptive  women  is  also 
a  source  of  danger  to  their  offspring.  Here,  perhaps,  is  a  cause  of 
infantile  tuberculosis.  We  say  "perhaps"  for  the  reason  that  the 
results  of  experimental  researches  have  thus  far  been  negative. 
Escherich  examined  the  milk  of  women  suffering  from  pulmonary 
tuberculosis,  but  he  was  unable  to  discover  any  bacilli.  It  seems, 
however,  that  he  did  not  make  inoculation  experiments.  In  1892 
Fecle  studied  the  question  more  thoroughly.1  He  injected  the  milk 
of  tuberculous  women  into  the  subcutaneous  cellular  tissue,  peri- 
toneum, and  anterior  chamber  of  the  eyes  of  rabbits  and  guinea-pigs, 
and  never  observed  the  development  of  tuberculosis.  These  results 
wrere  confirmed  by  Bonis.  The  experimental  inoculations  of  Bang 
wrere  likewise  negative.  The  author  observed  a  case  which  contra- 
dicted the  classical  opinion  and  showed  that  the  milk  of  a  con- 
sumptive ma3'  possibly  prove  virulent.2 

The  case  in  question  was  that  of  a  woman,  thirty-four  years  of 
age,  w7ho  entered  the  hospital  February  16,  1896,  for  a  pharyngeal 
tuberculosis.  She  was  pregnant,  and  confinement  occurred  under 
favorable  conditions.  From  that  moment  the  symptoms  became 
aggravated,  and  the  woman  died  on  the  24th  of  March,  seventeen 
days  after  childbirth.  The  necropsy  showed  advanced  tuberculous 
lesions  in  the  lungs  and  gray  granulations  in  the  liver,  kidneys,  and 
thyroid  gland. 

Two  days  after  birth  the  child  became  jaundiced,  and  then  green 

1  W.  Fcde.  Transmissibilita  della  tuberculosi  per  lattazione.  Congresso  pediatrico 
italiano.     (Anal,  in  Riforma  la  Medica,  1892,  vol.  iv.  p.  236.) 

2  Roger  et  Gamier.  Passage  du  bacille  de  Koch  dans  le  lait  d'une  femme  tuber- 
culeuse.     Soc.  de  biol.,  Feb.  24,  1900. 


ETIOLOQ  v  OF  INFECTIONS.  77 

diarrhea  and  edema  of  the  lower  extremities  supervened.  The 
infant  was  first  fed  from  the  bottle,  but  the  mother  undertook  to 
nurse  it  when  she  observed  thai  il  wag  ill.  Shegaveil  her  milk  from 
the  loih  to  the  L2th  of  March.  Aggravation  of  her  condition,  : 
ever,  prevented  her  from  further  suckling  her  offspring.  The  child 
lived  six  weeks.  At  the  necropsy  numerous  tubercles  were  di 
ered  in  the  liver,  spleen,  kidneys,  and  mesenteric  glands.  On  his- 
tological examination  of  the  liver  typical  tuberculous  granulations 
containing  Koch's  bacilli  were  found. 

On  March  11th,  four  days  after  confinement,  two  guinea-pigj  were 
inoculated  with  milk  taken  aseptic-ally  from  the  mother's  breast.  One 
guinea-pig,  weighing  440  grams,  received  I  c.cm.  of  the  milk  sub- 
cutaneously;  2  c.cm.  only  were  injected  into  the  peritoneal  cavity  of 
the  second  guinea-pig,  which  weighed  525  grams.  The  former 
animal  died  much  emaciated  on  the  14th  day  of  April,  and  at  the 
necropsy  presented  typical  lesions  of  generalized  tuberculosis.  The 
other  animal  survived.  It  weighed  565  grams  on  April  21st,  and 
050  grams  on  June  14th.  It  presented  hypertrophied  glands  in 
the  groin,  however.  It  was  killed  on  the  28th  of  the  following 
January.  At  the  necropsy  a  fibrous  peritonitis  was  found  at  the 
point  of  inoculation.  The  intestinal  coils  were  adherent  to  each 
other  and  to  the  lateral  wall  of  the  abdomen.  The  omentum  was 
thickened  and  contracted,  free  from  visible  tubercles.  The  rest  of 
the  abdomen  presented  no  lesions.  The  surface  of  the  liver  was 
studded  with  depressed  points  resembling  cicatrices.  Microscopic 
examination  of  the  viscera  showed  no  tuberculous  granulations, 
sclerotic  lesions,  or  bacilli. 

Of  the  two  guinea-pigs,  therefore,  only  one  became  tuberculous. 
The  one  which  received  the  larger  dose  of  the  milk  developed  tuber- 
culosis according  to  the  usual  mode,  and  death  occurred  in  thirty- 
three  days.  The  other  animal,  which  received  half  the  amount  of 
milk  injected  into  the  former  animal,  survived  and  seemed  to  be  in 
excellent  health  when  it  was  killed,  ten  months  after  inoculation. 
It  had  not,  however,  remained  absolutely  immune.  The  injected 
milk  had  not  acted  as  an  indifferent  liquid,  since  a  fibrous  peritonitis 
developed  at  the  point  of  inoculation,  and  thus  manifested  the  patho- 
logical process  that  had  taken  place  there.  Moreover,  a  hypertro- 
phied gland  in  the  groin  and  traces  of  cicatrices  upon  the  surface  of 
the  liver  proved  that  generalization  had  begun.  The  history  of  the 
first  guinea-pig  enables  us  to  explain  the  lesions  present  in  the  second 


78  ISFECTIO  US  DISEASES. 

animal.  In  the  former  the  quantity  of  injected  bacilli  was  large 
enough  to  overcome  the  resistance  of  the  organism,  and  tuberculosis 
was  generalized.  In  the  case  of  the  second  guinea-pig,  the  dose  being 
smaller,  infection  was  abruptly  arrested:  the  lesions  were  repaired 
and  common  cicatrices  only,  without  any  characteristic  elements,  were 
found. 

It  must  be  concluded  that  the  injected  milk  contained  bacilli, 
and  was,  therefore,  capable  of  transmitting  tuberculosis.  It  is  true 
the  child  was  exposed  to  sources  of  contamination  other  than  that 
of  suckling.  However,  as  the  necropsy  upon  the  child  showed  that 
the  lesions  predominated  in  the  mesenteric  glands,  liver,  and  spleen, 
it  is  probable  that  the  digestive  canal  was  the  principal  if  not  the 
only  route  of  contamination. 

Therefore,  the  milk  of  a  tuberculous  woman  may,  in  exceptional 
instances,  serve  as  a  vehicle  for  Koch's  bacillus  even  in  the  absence 
of  appreciable  tuberculous  lesions  in  the  mammary  glands. 

In  the  course  of  acute  infectious  diseases  the  milk  of  women  seems 
to  be  free  of  virulence.  The  unfavorable  results  of  artificial  feeding, 
especially  among  the  poorer  classes,  led  me  to  allow  sick  mothers  to 
nurse  their  children.  The  first  attempts  were  made  in  cases  of 
erysipelas,  the  writer  having  previously  learned  that  the  milk  con- 
tained no  streptococci.  Nine  children  were  suckled  by  the  mothers, 
three  others  were  allowed  mixed  alimentation  in  order  to  compen- 
sate for  the  diminished  amount  of  mother's  milk.  Under  these 
conditions  all  the  children  thrived. 

Suckling  was  likewise  continued  in  other  diseases.  Over  one  hun- 
dred women  suffering  from  measles,  scarlatina,  mumps,  or  sore 
throat  nursed  their  infants.  Among  these,  two  only  contracted 
measles,  and  then  only  in  a  very  mild  form.  This  immunity  of 
infants  leads  one  to  believe  that  the  milk  contains  immunizing  sub- 
stances from  the  very  beginning  of  the  mother's  illness.  Whatever 
the  correct  interpretation  of  the  fact  may  be,  the  innocuousness  of 
suckling  seems  to  be  well  established. 

Autoinfections. 

The  reality  of  morbid  spontaneousness  is  recognized  and  pro- 
claimed by  clinicians  as  is  that  of  contagion.  In  fact,  infectious  dis- 
eases are  seen  to  develop  without  any  accidental  contamination.  They 
occur  under  conditions  which  preclude  the  intervention  of  external 


ETIOLOGY  OF  INFECTIONS.  7!> 

germs.    When  an  Individual  baa  an  attack  of  pneumonia  ae  the 

result  of  exposure  to  cold,  w  <  • ;  h  times  search  in  vain  for  some  external 
origin  of  infection.  The  same  is  true  of  cases  of  sore  throat,  erysip- 
elas, osteomyelitis,  and  typhoid  fever,  in  which  the  minute  I  inquiry 
and  the  most  attentive  examination  fail  to  reveal  8  focus  oi  contam- 
ination. Therefore,  a  functional  disturbance  is  supposed  to  have 
been  produced  by  some  ordinary  cause. 

A  diametrically  contrary  view  arose  when  the  advances  of  bacte- 
riology revealed  the  animate  agents  of  infect 'mns.  Contamination  by 
a  certain  microbe  was  assumed  to  be  necessary  U>v  the  development 
of  every  case  of  infection  of  a  definite  character.  This  simple  theory 
was  not  in  harmony  with  clinical  observation.  The  enthusiasm 
aroused  by  new  discoveries  was  so  intense,  however,  that  the  unex- 
plained facts  of  clinical  observation  were  unhesitatingly  denied. 

Finally,  science  has  succeeded  in  harmonizing  the  contradictory 
and  exclusive  theories.  Morbid  spontaneousness  is  again  admitted. 
It  rests,  however,  upon  a  new  basis.  An  infectious  disease  often 
appears  to  be  due  to  a  series  of  microbes  which  constantly  reside 
upon  our  mucous  membranes  and  epidermis.  Under  normal  condi- 
tions the  organism  either  does  not  permit  these  dangerous  guest-  to 
penetrate  into  its  interior,  or  it  rapidly  destroys  those  which  pass 
the  epithelial  barriers.  When,  however,  the  organism  is  disturbed 
by  some  influence,  the  microbes  invade  it.  Infection  is  then  justly 
said  to  have  been  spontaneous — i.  c,  to  have  developed  without  any 
outward  contamination . 

Distribution  of  Microbes  within  the  Normal  Organism.  It  is 
readily  understood  that  microbes,  being  abundantly  distributed 
around  us,  must  necessarily  be  encountered  on  every  part  of  our 
organism  in  contact  with  the  external  world. 

At  each  inspiration  a  certain  number  of  bacteria  are  carried  with 
the  air  into  the  respiratory  passages.  They  are.  however,  arrested 
in  their  course  by  various  organs:  by  the  hair  in  the  nasal  cavities, 
by  the  vibrotile  cilia  of  the  bronchial  mucous  membrane,  and  by  the 
secretions,  so  that  the  air  is  often  bacteriologically  pure  in  the  pul- 
monary alveoli  and  even  in  the  bronchioles.  In  sweeping  back 
through  the  respiratory  tract  the  air  does  not  take  up  any  germs  once 
deposited,  since,  as  has  already  been  stated,  microbes  can  never 
leave  liquid  media.     The  expired  air.  therefore,  contains  no  bacteria. 

The  respiratory  apparatus  is  happily  provided  with  various  means 
of  protection  against  microbes.     The  secretions  act  mechanically. 


80  INFEt ' TIO  US  DISEASES. 

and,  so  to  speak,  wash  the  mucous  membrane.  A  certain  number 
of  bacteria  are  thus  thrown  out,  others  are  destined  by  the  nasal 
mucus,  which  possesses,  as  Lermoyez  and  Wurtz  have  shown,  a  ger- 
micidal power,  viz.,  exert  a  sort  of  antiseptic  action.  The  remainder 
is  incorporated  and  devoured  by  phagocytes  which  greatly  abound 
in  the  pulmonary  alveoli  and  wherever  lymphoid  tissue  is  highly 
developed. 

Bacteria  are  found  in  far  larger  numbers  in  the  alimentary  canal. 
The  buccal  cavity  contains  the  most  varied  species,  among  which 
some  endowed  with  pathogenic  properties  are  almost  constantly 
present.  Such  are  the  pneumococcus,  the  streptococcus,  and  the 
micrococcus  tetragenus.  The  gastric  juice  has  not  such  germicidal 
power  as  was  formerly  believed,  since  recent  enumerations  demon- 
strate that  this  portion  of  the  alimentary  tract  contains  large  num- 
bers of  bacteria,  even  more  than  the  duodenum. 

The  microbes  find  in  the  intestines  conditions  most  favorable  to 
their  existence.  They  are  in  nowise  disturbed  by  the  secretions 
elaborated  there,  and  they  find  an  abundant  supply  of  food.  It 
may,  therefore,  be  said  that  the  intestine  is  the  paradise  of  microbes. 
The  following  figures,  borrowed  from  the  interesting  contributions 
•of  Gilbert  and  Dominici,  show  how  well  they  thrive  there :  50,000 
microbes  per  cubic  millimetre  are  found  in  the  stomach.  In  the  first 
part  of  the  duodenum  the  number  is  only  30,000  per  cubic  milli- 
metre. From  this  point  the  number  progressively  increases  until 
the  lower  portion  of  the  intestine  is  reached,  where  the  maximum 
number,  100,000  per  cubic  millimetre,  is  found.  In  the  cecum 
another  fall  occurs,  and  throughout  the  large  intestine  the  number 
is  25,000  to  30,000  per  cubic  millimetre.  When  the  quantity  of  fecal 
matter  contained  in  the  alimentary  canal  is  taken  into  account,  the 
remarkable  total  of  411,000,000,000  of  microbes  is  reached. 

The  digestive  tract  is  protected  against  microbes  in  the  same 
manner  as  in  other  parts  of  the  organism.  The  intestinal  and  pan- 
creatic juices  and  the  bile,  though  possessing  no  germicidal  power, 
serve  to  sweep  away  and  expel  both  microbes  and  their  toxins. 
Those  micro-organisms  which  pass  through  the  mucous  membrane 
are  arrested  by  the  lymphoid  structures,  follicles,  and  glands  of 
Peyer,  and  by  the  numerous  leucocytes  which  are  constantly  wan- 
dering in  this  region  and  may  even  enter  the  cavity  of  the  intestine. 
Should  any  microbes  escape  these  agents  of  destruction  they  are  ar- 
rested in  the  lymphatic  glands  and  in  the  liver,  where  new  defensive 


ETIOLOGY  OF  INFECTIONS.  81 

measures  are  united.    Should  i  hey  pass  furl  her,  they  reach  the  lu 
which  are  likewise  endowed  with  germicidal  power.     We  thu 

how  numerous  arc  I  he  defenses  provided  io  antagonize  i  he  intestinal 
microbes,  since  the  danger  of  invasion  of  the  economy  by  resident 
microbes  is  Found  especially  in  the  alimentary  canal. 

The  genito-ujinary  organs  also  contain  bacteria,  al  Least  in  their 
external  portions.  The  researches  of  Stroganoff,  Menge,  and  Kroe- 
nig  have  shown  that  the  vaginal  secretion  is  richly  endowed  with 
germicidal  properties.  If  some  inoffensive  bacterium,  such  as  the 
bacillus  pyocyaneus,  or  a  pathogenic  micro  organism,  such  as  the 
streptococcus  or  the  staphylococcus  aureus,  is  deposited  deep  within 
the  vagina  they  are  soon  destroyed. 

With  regard  to  the  urinary  passages,  it  is  admitted  that  bacteria 
do  not  ascend  the  urethra  and  never  penetrate  the  bladder,  and  since 
the  time  of  Pasteur  it  has  repeatedly  been  stated  that  urine  voided 
aseptically  does  not  decompose.  Recent  researches,  however,  tend 
to  demonstrate  that  such  is  not  always  the  case.  The  investigation- 
of  Lustgarten,  confirmed  by  those  of  Dr.  Courtois  in  our  laboratory, 
show  that  the  urine  of  healthy  individuals  frequently  contains  micro- 
organisms. Lustgarten  describes  eleven  species,  one  of  them  very 
peculiar,  namely,  the  streptococcus  giganteus  urethras,  the  chains  of 
which  are  composed  of  several  hundreds  and  even  more  than  a  thou- 
sand individual  cocci.  The  length  of  the  chain  is  equal  to  five  or 
six  times  the  diameter  of  the  field  of  the  microscope.  This  strep- 
tococcus is  not  pathogenic  for  rabbits.  Five  cubic  centimetres  of  a 
bouillon  culture  was  injected  into  the  veins,  and  in  order  to  render 
its  action  more  efficacious  we  at  the  same  time  introduced  1  c.cm.  of 
a  sterilized  culture  of  bacillus  prodigiosus.  The  result  was  negative, 
since  the  animal  manifested  no  disturbance. 

Autogenic  Infections.  Of  the  microbes  which  are  found  in  living 
organisms  under  normal  conditions,  some  always  remain  harmless; 
others  become  pathogenic  as  soon  as  some  unfavorable  occur- 
rence weakens  the  resistance  of  the  economy.  They  can  then  pene- 
trate the  barriers  and  give  rise  to  various  lesions.  Upon  the  skin 
acne,  furuncles,  anthrax,  and  at  times  gangrene  or  erysipelas  appear. 
In  the  buccopharyngeal  cavity :  anginas  and  phlegmons  of  the  tonsils. 
in  the  respiratory  apparatus:  bronchites.  bronchopneumonias,  and 
fibrinous  pneumonia;  in  the  intestines:  diarrhea,  either  simple, 
choleriform,  or  dysenteriform,  etc.,  occur.  The  microbes  may  also 
secondarily  or  primarily  invade  the  organism  at  large  and  produce 

6 


82  INFECTIOUS  DISEASES. 

septicemia  or  pyemia,  and  thus  give  rise  to  numerous  visceral 
lesions. 

In  this  connection,  typhoid  fever  requires  special  consideration. 
As  soon  as  an  epidemic  of  this  disease  breaks  out,  the  drinking  water 
is  subjected  to  minute  examination,  and  if  a  bacillus  more  or  less 
analogous  to  that  of  Eberth  is  encountered,  the  entire  etiological 
problem  is  believed  to  be  solved.  We  are  told  that  improved  canali- 
zation and  pure  water  supply  are  the  best  means  to  overcome  a 
typhoid  epidemic,  and,  in  many  instances,  practice  has  amply  justi- 
fied this  theory. 

Some  epidemiologists,  however,  refuse  to  accept  a  theory  so  exclu- 
sive. The  penetration  of  the  bacillus  into  the  organism  does  not 
seem  to  them  sufficient  to  elucidate  the  etiology  of  typhoid  fever. 
Army  physicians,  who  are  usually  in  a  position  to  follow  the  course 
of  epidemics,  constantly  protest  against  the  exaggerations  of  some 
authorities. 

Dr.  Arnold  in  an  article  in  the  Dictionnaire  encyclopedique,  and  Dr. 
Kelsch,1  in  his  treatise  on  epidemiology,  seem  to  have  gone  to  the 
root  of  the  question. 

In  view  of  the  great  readiness  with  which  typhoid  fever  makes  its 
appearance  as  a  result  of  overwork,  and  especially  under  conditions 
of  overcrowding,  such  as  exists  in  the  case  of  armies  in  camp,  it  may 
well  be  questioned  whether  man  does  not  carry  within  himself  the 
germ  of  the  disease,  and  whether  external  contamination  is  really 
necessary. 

Kelsch2  fully  demonstrates  that  the  role  of  overfatigue  and  of 
crowding  are  potent  etiological  factors.  These  bring  in  their  train 
contamination  of  the  soil  and  water.  Typhoid  fever,  therefore, 
invariably  appears  in  camps,  and  particularly  in  permanent  camps, 
at  the  end  of  five  or  six  weeks,  when  the  men  are  exhausted  by  over- 
work. It  may  be  objected,  however,  that  some  of  the  men  were  sick 
when  they  left  the  city,  or  that  the  disease  was  in  the  stage  of  incu- 
bation. It  is  necessary,  however,  to  pile  up  a  good  deal  of  the  most 
hypothetical  reasoning  in  order  to  support  the  dogma  of  morbid 
specificity.  The  etiology  becomes  singularly  simplified  and  rational 
when  the  malady  is  attributed  to  endogenic  origin,  that  is  to  auto- 
infection,  or,  in  other  words,  when  it  is  assumed  that  men  carry  the 
germs  of  the  malady  in  the  form  of  saprophytes,  and  that  overwork, 

1  Kelsch.    Traite  des  maladies  epiderniques,  Paris,  1894.  2  Ibid. 


ETIOLOQ  v  OF  INFECTIONS.  83 

by  diminishing  their  vital  existence,  permit  the  transformation  of 
these  saprophytes  into  pathogenic  agenl  i. 

Admitting,  however,  i  li;ii  an  animate  agenl  i  indi  pensable  f or  the 
production  of  an  infectious  disease,  and  thai  there  are  two  orders 

of  microbes  specific  ;nnl  imn  specific  the  question  ari  e  :  to  which 
order  does  the  microbe  of  typhoid  fever     Eberth'j  bacilluf     belong? 

Most  bacteriologists  answer  thai  il  belongs  to  the  specific  order. 
Drs.  Rodet  and  Roux  have  advanced  a  contrary  opinion.  According 
bo  bhem  the  typhoid  bacillus  is  bul  a  variety  of  colon  bacillus.  As 
is  known,  this  theory  provoked  a  greal  deal  of  controversy.  In  fact, 
confidence  was  gradually  lessened  as  to  the  destructive  character  of 
Eberth's  bacillus,  as  the  hitler  was  proved  to  have  no  absolute  value. 
Most  recent  researches,  however,  have  furnished  ;i  new  method  for 
recognizing  the  typhoid  bacillus.  The  serum  of  an  animal  that  has 
been  vaccinated  against  a  duly  verified  specimen  of  this  microbe  is 
employed  and  its  agglutinating  action  noted  upon  the  bacillus  which 
is  to  be  identified.  By  the  employment  of  this  method,  which  seems 
to  be  unassailable,  Drs.  Remlinger  and  Schneider1  demonstrated  the 
presence  of  the  typhoid  bacillus  in  water  obtained  far  from  epidemic 
foci,  in  the  soil,  and,  what  is  of  far  greater  consequence,  in  the  ali- 
mentary canal  of  individuals  free  from  typhoid  fever.  The  last  fact 
is,  as  has  been  said,  of  considerable  interest,  since  it  explains  pre- 
viously obscure  facts  and  harmonizes  bacteriology  and  epidemiology. 
Dr.  Kelsch  is,  therefore,  right  in  stating,  according  to  the  data  of 
clinical  observation,  that  typhoid  fever  may  be  produced  by  germs 
carried  in  our  bodies  and  which,  although  harmless  saprophytes 
under  ordinary  conditions,  temporarily  manifest  virulent  functions 
under  the  influence  of  marked  violations  of  hygiene,  notably  pro- 
longed fatigue,  defective  regimen,  ordinary  pollution  of  water — all 
circumstances  which,  by  virtue  of  their  combination,  are  so  powerful 
in  creating  a  putrid  state  in  the  internal  medium.2 

Such  is  the  rational  conception  which  we  may  at  present  form  with 
regard  to  the  etiology  of  typhoid  fever.  It  is  the  view  which  I  have 
advocated,  in  a  study  made  some  years  ago.3  These  ideas,  which 
were  described  in  detail  by  Dr.  Bourgeois,4  aroused  bitter  criticism. 

1  Remlinger  et  Schneider.  Contribution  a  l'etvuie  du  baeille  typhique.  Arm.  de  l'ln- 
stitut  Pasteur,  January,  1S07. 

2  Kelsch.     Loc.  cit.,  p.  463. 

3  Roger.  Etiologie  et  pathogenic  do  la  fievre  typho'ide.  Presje  medieale.  March  17, 
1S94. 

4  Bourgeois.     Etiologie  et  pathogenic  de  la   fievre  typhoide.     The<e  de  Pari?.  1  - 


84  ISFECTIO  US  DISEASES. 

The  discovery  of  Drs.  Remlinger  and  Schneider  demonstrates  beyond 
all  doubt  the  truth  of  the  view  to  which  I  was  led  by  an  impartial 
study  of  typhoid  epidemics. 

The  Autogenous  Origin  of  Various  Specific  Infections.  Among 
other  diseases  which,  perhaps,  at  times  appear  spontaneously,  diph- 
theria should  first  be  mentioned.  Bacteriology  has  already  estab- 
lished the  presence  in  the  mouth  of  a  bacillus  analogous  to  that 
discovered  by  Loeffler.  Does  this  non-virulent  pseudodiphtheria 
bacillus  represent  an  attenuated  variety  or  a  distinct  species? 
This  is  an  important  and  as  yet  unsolved  problem.  Likewise  the 
spontaneous  origin  of  gonorrhea  cannot  be  admitted  except  with 
the  greatest  reservation,  viz.,  its  appearance  in  the  absence  of  sexual 
intercourse,  as  in  the  well-known  observation  of  Straus. 

It  may  be  asked  wdiether  the  germs  of  the  eruptive  fevers  are  not 
often  present  in  the  bodies  of  healthy  individuals.  My  personal 
statistics,  covering  304  cases  of  measles,  340  of  scarlatina,  69  of 
varicella,  and  38  of  variola,  show  that  in  a  great  number  of  cases 
the  minutest  inquiry  fails  to  reveal  any  mode  of  contamination. 
We  merely  present  the  question  of  the  autogenous  origin  of  these 
various  affections.  A  decision  must  be  reached  through  bacterio- 
logical investigation.  In  the  case  of  eruptive  fevers  it  may  be  as- 
sumed that  the  mode  of  contamination  is  so  often  uncliscoverable 
because  their  germs  are  perhaps  widely  distributed  and  because 
some  of  these  fevers,  particularly  measles,  are  contagious  in  the 
prodromic  stage,  previous  to  all  serious  manifestations,  when  con- 
tact is  scarcely  noticed. 

Auxiliary  Causes  of  Infections. 

Meteorological  and  Seasonal  Influences.  The  role  of  cosmic 
influences  has  at  all  times  been  accepted.  This  is  evidently  due  to 
the  fact,  which  is  open  to  popular  observation,  that  the  frequency 
of  infections  is  subject  to  quite  regular  oscillations  each  year.  The 
accompanying  table  gives  a  resume  of  my  personal  statistics,  and 
shows  plainly  that,  each  year,  infectious  morbidity  runs  nearly  a 
parallel  course.  The  minimum  is  observed  in  October  and  Novem- 
ber. Then  follows  an  increase  which  reaches  the  maximum  in  the 
spring,  from  April  to  June  or  July.  The  figures  of  each  year  are 
almost  the  same.  It  is  to  be  noted  that  measles  appears  earlier  in 
the  year  than  scarlatina,  and  reaches  the  highest  point  in  April  and 
May.     On  the  other  hand,  scarlatina  increases  until  June.    Although 


ETIOLOO  V  OF  INFECTIONS. 

less  pronounced,  variations  of  anginai  of  diphtheritic  or  other  type 
are,  nevertheless,  clear. 


Measles. 

L896 

1897 

L898 

L900 

Number  of  cases  « •  I »  erved  . 

804 

:;7U 

398 

370 

1817 

Oases  with  contagion  . 

7!» 

s:: 

71 

89 

Percentage 

25.1 

•J  l  ,8 

24 

17 

„'l  :: 

1  'i-ici-iil.iyc    i n 

L9.5 

is.:; 

WIS 

21 

13 

17  8 

"                women 

::n  l 

21.6 

J'i  il 

i\ 

17.6 

"                i  he  ii'-\i  born 

31.9 

J7.!l 

20 

25.7 

Satr/atitHi. 

Number  of  cases  observed    . 

:',  in 

mi 

l'ir, 

770 

l::7 

2213 

Cases  with  contagion   . 

.".:; 

18 

75 

174 

53 

373 

Percentage 

L5.5 

1  II 

15.1 

22.3 

12  1 

li,  - 

Percentage    in    men 

8.0 

6.2 

9.7 

10 

L2  6 

l  j  .". 

"                     women 

21.1 

14.4 

19 

25 

20.1 

Varicella . 

Number  of  cases 

69 

52 

45 

32 

117 

:',  1 5 

Cases  with  contagion  . 

23 

14 

'.) 

1 

44 

'H 

Percentage 

33.3 

20.9 

20 

:;.l 

37.0 

J-  - 

Variola. 

Number  of  cases 

38 

20 

2 

1 

928 

989 

Cases  with  contagion  . 

14 

8 

1 

1 

246 

•_'7<  i 

Percentage 

36.8 

40 

50 

100 

20.5 

27.3 

The  greatest  number  of  cases  of  this  kind  are  observed  in  May  and 
June.  It  is  to  be  noted  also  that  mumps  is  particularly  prevalent 
in  April  and  May,  and  seldom  occurs  during  the  months  of  October 
and  November. 

In  this  connection  smallpox  is  a  remarkable  exception.    The  c 
occur  with  nearly  the  same  frequency  throughout  the  year. 

In  the  author's  table  the  figures  for  erysipelas  are  those  of  the  year 
1900  onty.  The  variations  here  shown,  however,  are  entirely  com- 
parable to  those  occurring  in  the  eruptive  fevers. 

The  influence  of  seasons  is  doubtless  ascribable  to  manifold  car,-  - 
thermometric,  barometric,  and  hygrometric  variations,  the  action 
of  the  sun,  rain,  wind,  and  thunder-storms,  and  the  role  of  ozone  are 
causes  readily  perceived.  Do  these  influences,  however,  affect  the 
morbid  germs  or  the  higher  organisms?  Both  hypotheses  have 
equally  competent  defenders.  It  seems  that  the  lower  the  animal  or- 
ganism, the  better  it  resists  cosmic  variations.  Variations  in  pressure 
and  temperature  which  would  rapidly  kill  a  mammalian  act  indif- 
ferently upon  bacteria.  It  is  more  likely,  therefore,  that  the  recep- 
tivity of  the  human  organism  is  modified  by  disturbing  meteoric 
causes.  It  is  difficult,  however,  to  further  elucidate  this  rather  vague 
problem.     All  that  can  be  added  is  the  fact  that  respiratory  disturb- 


86  IXFECTIO  US  DISEASES. 

ances  are  especially  frequent  when  variations  of  temperature  occur 
and,  principally,  in  the  spring.  Thoracic  complications  in  the  course 
of  infections  such  as  erysipelas  and  variola  are  almost  always  ob- 
served during  the  period  from  the  month  of  March  to  the  month  of 
May.  On  the  other  hand,  heat  favors  the  genesis  of  gastrointestinal 
affections. 

After  the  monthly  variations,  those  embracing  longer  periods  must 
be  considered.  Variations  in  the  cases  of  smallpox  may  be  due  to 
negligence  in  the  matter  of  vaccination.  It  is  difficult,  however,  to 
account  for  the  changes  occurring  in  a  disease  like  scarlet  fever. 
A  tabulation  of  our  cases  from  1896  to  1900  shows  the  number  of 
cases  increasing  progressively  from  161  to  496,  reaching  a  maximum 
of  779,  and  then  suddenly  declining  to  437.  It  is  curious  to  note 
that  the  variations  in  anginas  correspond  exactly  to  those  occurring 
in  scarlatina.  The  eminent  role  of  sore  throat  in  the  symptoma- 
tology of  scarlatina  lends  a  certain  interest  to  this  parallelism. 
Measles,  on  the  contrary,  presents  almost  no  variation.  On  an 
average,  we  receive  from  360  to  380  cases  annually.  As  in  the  case 
of  frequency,  the  gravity  of  cases  undergoes  periodical  variations. 
The  history  of  scarlatinal  epidemics  observed  in  England  and  of 
epidemics  studied  by  Bretonneau  in  Tours  clearly  demonstrates  this. 

The  influence  exerted  by  climate  is  still  more  marked  than  in  the 
case  of  seasons.  There  are  countries  in  which  certain  infectious  dis- 
eases cannot  become  acclimated.  Yellow  fever,  which  claims  so 
many  victims  in  certain  portions  of  the  new  world,  seldom  appears 
on  the  old  continent. 

In  this  respect  the  sanitary  conditions  of  a  country  are  of  the 
greatest  importance.  The  number  of  infectious  cases  has  consid- 
erably diminished  since  the  advance  of  disinfection,  the  creation  of 
special  hospitals  for  the  isolation  of  contagious  cases,  and  the  im- 
provement of  drinking  water.  Even  typhoid  fever  is  at  present  less 
frequent. 

Influence  of  Race  and  of  Family.  Morbid  receptivity  varies  con- 
siderably in  different  races.  The  negroes  are  immune  from  certain 
infections,  such  as  yellow  fever,  and  very  seldom  suffer  from  ma- 
laria.    On  the  other  hand,  they  are  very  susceptible  to  tetanus. 

The  yellow  race  is  predisposed  to  variola,  which  prevails  in  China 
in  an  endemic  form. 

Acute  articular  rheumatism  is  confined  almost  exclusively  to  the 
Caucasian  race. 


ETIOLOQ  V  OF  INFECTIONS. 


87 


If   we  pass  from  race  to  family  we  encounter  analogou 
There  are  families  particularly  sensitive  to  tuberculosi  .  or  diphthe- 
ria, or  erysipelas.     From  this  point  of  view  I  have  questioned  956 
men  and  KM  I  women  suffering  from  erysipela  .     Many  of  them  were 
incapable  of  giving  any  information.    Taking  into  account ,  how< 
flic  accurate  replies,  I  liml  iliat  erysipelas  existed  in  the  familii 
94  men  and  L10  women,  which  gives  a  ratio  of  9.8  per  LOO  for  the 
former  and  L0.5  for  the  latter.    Simple  coincidence  does  qoI  ade- 
quately account  for  so  high  a  proportion.    Moreover,  our  figures 
below  the  actual  number,  as  many  patients  were  unable  to  state 
whether  their  parents  had  ever  had  an  attack  of  erysipelas.    The 
following  table  gives  the  family  history  of  this  affection  and  .-hows 
that,  in  many  instances,  the  parents  had  several  attacks  and  the 
malady  ran  through  several  generations: 


I'm .  nis  having  ■ 

II,,, 


Father 

Mother 

Father  and  mother 

Grandmother 

Grandmother  and  father 

Grandmother  and  mother 

Brother  or  sister 

Father  and  brother 

Mother  and  sister 

Uncle  and  aunt  . 

Children     . 


21 

8 

54 

37 

2 

3 

7 

11 

7 

2 

7 

3 

22 

17 

22 

1 

3 

1 

4 

5 

3 

5 

152 


In  the  majority  of  cases  contagion  is  not  to  be  thought  of,  for  the 
children  were  either  far  removed  from  the  parents  or  erysipelas 
appeared  after  the  death  of  the  latter.  One  of  the  most  curious 
observations  in  this  respect  is  that  of  a  man,  fifty-five  years  of  age. 
whose  mother  had  experienced  twelve  attacks  of  erysipelas.  He, 
himself,  was  suffering  from  his  fourteenth  attack.  While  he  was 
under  treatment  in  our  wards,  his  son,  who  was  enlisted  in  a  regi- 
ment of  dragoons  in  Sedan  and  had  not  seen  his  father  for  over  six 
months,  had  his  first  attack  of  facial  erysipelas.  On  other  occasions 
I  observed  two  sisters  who,  although  not  residing  together,  synchro- 
nously contracted  facial  erysipelas,  and.  what  was  more  curious,  the 
affection  assumed  a  wandering  course  in  both,  and  invaded  the 
greater  part  of  the  trunk. 

It  seems  that  the  streptococcus,  like  many  other  microbes,  finds 
in  certain  families  a  soil  particularly  favorable  for  its  development. 


88  INFEQTIO  US  DISEASES. 

Individual  Immunity  and  Predisposition.  There  are  numerous 
individual  variations;  some  persons  have  often  exposed  themselves 
to  contagion,  even  to  vaccination,  without  being  contaminated.  A 
great  number  of  cases  have  been  reported  in  which  vaccination  has 
not  taken.  The  same  thing  is  at  times  observed  in  laboratories. 
One  animal  resists,  while  others,  apparently  similar,  placed  under 
identical  conditions  and  inoculated  in  the  same  manner,  die  without 
exception. 

In  some  cases,  insensible  gradual  vaccination  may  account  for 
individual  immunity.  The  natives  of  Paris,  for  instance,  do  not,  as 
a  rule,  contract  typhoid  fever,  which  does  not  spare  all  individuals 
arriving  from  the  country.  The  reason  is  that  Parisians  from  their 
infancy  have  been  little  by  little  impregnated  with  the  germ.  Thus 
becoming  gradually  habituated,  they  have  either  suffered  no  distur- 
bance or  manifested  symptoms  too  mild  and  vaguely  characterized 
to  be  traced  to  their  true  course. 

Insensible  vaccination  also  explains  the  disappearance  of  epi- 
demics. If,  at  a  given  time,  the  cases  diminish  in  number  and  sever- 
ity, this  is  clue  to  the  fact  that  the  population  has  slowly  been 
subjected  to  insensible  vaccination.  The  immunity  of  physicians  is 
clue  to  no  other  cause. 

The  fact  that  an  infection  loses  its  gravity  in  the  course  of  cen- 
turies, or  acquires  unusual  malignancy  when  it  invades  a  people  until 
then  immune,  may  be  attributed  to  an  analogous  process.  The 
epidemics  of  measles  in  the  Faroe  Islands  clearly  illustrate  this  fact. 
The  disease  was  imported  into  these  islands  in  1846.  Of  the  7782 
inhabitants,  6000  were  attacked,  the  aged  alone  being  spared.  In 
1875  the  same  malady  invaded  the  Fiji  Islands  and  killed  40,000 
persons  out  of  a  population  of  150,000. 

Influence  of  Age,  Sex,  and  Accidental  Disturbances.  Morbid 
aptitude  varies  considerably  with  age.  During  intrauterine  life  the 
fetus  is  exposed  to  some  diseases  the  germs  of  which  are  transmitted 
through  the  placenta.  At  the  time  of  birth  the  individual  offers 
sufficient  resistance  to  the  majority  of  infections;  vaccination  does 
not  take,  eruptive  fevers,  as  well  as  typhoid  fever  and  diphtheria,  are 
altogether  exceptional.  On  the  other  hand,  erysipelas,  which  is  gen- 
erally localized  in  the  navel  and  almost  invariably  proves  fatal,  is 
very  readily  contracted  by  the  newborn. 

Infectious  diseases  are  frequent  during  childhood.  At  this  epoch 
of  life  the  tissues  are  particularly  apt  to  permit  the  development  of 


ETIOLOGY  OF  INFECTIONS. 


89 


parasites.     Pityriasis,  for  instance,  doc-;  not  thrive  in  the  aged,  and 
spontaneously  disappears  with  the  advance  of  year 
The  frequency  of  infections  diminishes  with  age.     In  the  aged 

scarcely  any  other  disorders  than  vesical  infection    and  pneumonia 
occur.     Does  (lie  immunity  of  old  age  depend  upon  previous  di  i 
and  insensible  vaccination?    Not  altogether.     A  certain  influence 

must,  be  attributed  to  the  modifications  produced  in  the  chemical 
constitution  of  the  tissues  and  humors.  This  is  proved  by  the  fad 
that  when  measles  invaded  the  Faroe  Islands  only  the  aged  were 
spared  by  the  disease,  which  was  unknown  up  to  that  time. 

The  influence  of  sex  is  no  less  interesting.  It  seems  thai  women 
are  predisposed  to  the  infections  of  childhood  for  a  longer  period  than 
men.  The  eruptive  fevers,  which  are  <|uite  rare  among  men  after 
the  age  of  twenty  years,  are  frequently  observed  among  women 
between  twenty-five  and  thirty  years  of  age. 

The  following  table  presents  the  results  of  my  personal  observa- 
tions from  this  point  of  view: 


Measles. 

Men. 

Women. 

Tola' 

Before  2 

years 

.      160 

194 

354 

2  to  14 

years 

.      119 

122 

241 

15  to  20 

" 

.      300 

224 

524 

21  to  25 

it 

128 

247 

375 

26  to  30 

" 

82 

120 

202 

31  to  35 

" 

3S 

42 

so 

36  to  40 

" 

13 

16 

29 

41  to  45 

" 

4 

5 

9 

46  to  50 

" 

1 

1 

2 

51  to  60 

" 

1 

1 

Total 

846 

971 

1S17 

Adults 

above  15  years 

Scarlatixa. 

567 

655 

1222 

Men. 

Women. 

Total. 

Before  2 

years 

29 

27 

56 

2  to  14  years 

.      22S 

202 

430 

15  to  20 

tt 

.      388 

369 

757 

21  to  25 

ti 

167 

33S 

505 

26  to  30 

n 

So 

167 

252 

31  to  35 

" 

44 

82 

1 26 

36  to  40 

" 

19 

29 

4-- 

41  to  45 

tt 

9 

s 

17 

46  to  50 

" 

4 

8 

12 

51  to  60 

" 

2 

8 

10 

Total 

.      975 

1238 

2213 

Adults 

above  15  years 

71S 

1000 

1727 

90 


INFECTIOUS  DISEASES. 


V  UUCELLA 


Before  2  years 
2. to  14  years 
15  to  20  ,  •■ 
21  to  25  " 
26  to  30  " 
31  to  35  " 
36  to  40  " 
41  to  45  " 
46  to  50      " 

Total 

Adults  above  15  years 


Before  2  years 
2  to  14  years 
15  to  20  " 
21  to  25  " 
26  to  30  " 
31  to  35  " 
36  to  40  " 
41  to  45  " 
46  to  50  " 
51  to  60  " 
61  to  91       ', 

Total 

Adults  above  15  vears 


Variola. 


Mai. 

Women. 

Total. 

57 

46 

103 

69 

54 

123 

IS 

10 

34 

17 

10 

27 

S 

6 

14 

4 

3 

7 

2 

2 

4 

2 

2 

1 

1 

176 

139 

315 

50 

39 

S9 

Men. 

Women. 

Total 

20 

12 

32 

40 

22 

62 

SS 

59 

147 

80 

105 

185 

50 

105 

155 

56 

71 

127 

45 

55 

100 

27 

28 

55 

22 

24 

46 

20 

29 

49 

16 

15 

31 

464 

525 

989 

404 

491 

895 

These  figures  show  the  influence  of  sex  and  age  upon  the  frequency 
of  the  eruptive  fevers.  From  fifteen  to  twenty  years  of  age  measles 
and  scarlatina  are  more  frequent  among  men  than  women.  At 
twenty  they  undergo  a  sudden  fall  in  the  male  sex,  while  among 
women  they  remain  at  a  very  high  level. 

The  study  of  variola  shows  plainly  the  beneficial  influence  of  vac- 
cination. Children  are  not  frequently  attacked.  The  disease  in- 
creases after  the  age  of  fifteen  years.  The  maximum  for  men  is 
reached  from  fifteen  to  twenty  years  of  age.  Among  women  the 
frequency  increases,  exceeds  that  of  the  other  sex,  and  remains  high 
from  twenty-one  to  thirty  years  of  age. 

The  variations  according  to  sex  are  less  marked  for  the  other 
infections.  Thus,  the  author  found  that  134  men  and  122  women 
were  attacked  by  diphtheria,  and  385  men  and  407  women  by 
anginas.  According  to  the  author's  statistics,  mumps  seems  to  be 
more  frequent  among  men  than  women,  as  he  has  found  170  of  the 
former  and  only  65  of  the  latter  affected  with  this  disease.  This 
result  is  probably  due  to  the  greater  gravity  of  the  disease  in  men 


ETIOLOGY  OF  INFECTIONS.  '.>] 

and  to  the  frequency  of  orchitis  which  compel    them  to  enter  the 
hospital. 

The  different  acts  of  genital  life  invesl  feminine  pathology  with  8 
peculiar  ('li:ii-:icici-.     Menstruation  may  be  an  occasional  can 
infectious  manifestations.    Such,  especially,  is  the  case  in  erysip 
an  attack  of  which  may  attend  each  period.    Certain  women  thus 
experience  fifty  and  sixty  relapses. 

Pregnancy  m;i.y  modify  I  he  course  of  certain  infections.  Not  infre- 
quently tuberculosis  seems  to  be  arrested  and,  after  confinement,  the 
disease  assumes  a,  more  rapid  course  ll  is  hardly  necessary  to  refer 
to  the  frequency  of  puerperal  infections.  In  this  case,  however,  the 
diseases  present  nothing  special.  The  puerperal  woman  ie  in  the 
same  situation  as  a  wounded  one 

All  violations  of  the  laws  of  hygiene  predispose  to  infection-.  The 
noxious  effects  of  overcrowding  have  already  been  referred  to.  The 
influence  of  previous  diseases  is  well  known.  Some  of  them  predis- 
pose to  infections.  Diabetes  favors  the  development  of  pyogenic 
microbes  and  of  the  tubercle  bacillus.  Pneumonia,  erysipelas,  and 
rheumatism,  far  from  conferring  immunity,  predispose  to  new 
attacks.  As  a  rule,  however,  infections  create  a  refractory  state  and 
prevent  future  attacks.  It  is  well  to  add,  however,  that  immunity 
is  in  no  case  absolute  except,  possibly,  in  syphilis. 

Among  causes  which  lessen  individual  resistance,  the  influence  of 
external  agents  is  of  chief  importance.  Serious  traumatism,  crush- 
ings,  and  extensive  contusions  diminish  considerably  the  resistance 
to  invasion  by  microbes. 

The  action  of  cold  and  heat  is  very  complex,  for  they  do  not  act 
simply  by  modifying  the  temperature  of  the  body.  The  fact  that 
chickens,  which  are  naturally  immune  to  anthrax,  contract  this  infec- 
tion when  they  are  exposed  to  cold,  and  that,  on  the  contrary,  frogs 
lose  their  immunity  when  exposed  to  high  temperatures,  is  not  due 
to  modifications  of  the  organic  temperature  thus  produced  in  these 
animals.  In  reality  the  phenomena  are  more  complex.  When 
chickens  are  exposed  to  cold  and  frogs  to  heat,  nutrition  is  disturbed: 
the  life  of  the  cells,  and  consequently  the  constitution  of  the  humors, 
is  altered;  the  heart,  the  nervous  system,  and  the  leucocytes  are  acted 
upon.  Abolition  of  immunity  is,  therefore,  the  result  of  manifold 
factors. 

Action  of  Poisons  upon  Infections.  A  great  number  of  poisons 
diminish    the    resistance    of    the   organism   to   infectious    agents. 


92  LXFECTIOUS  DISEASES. 

Seeck  noticed  that  various  parasites  developed  upon  the  skin  of  frogs 
treated  with  metallic  poisons.  Some  of  the  lesions  observed  in  the 
course  of  intoxications  are  in  reality  due  to  secondary  infection. 
Such  is  the  case  in  mercurial  stomatitis  or  enteritis.  The  mercury 
during  elimination  by  the  mucous  membranes  denudes  the  latter  of 
their  epithelium  and  prevents  them  from  resisting  invasion  by  the 
numerous  microbes  swarming  upon  their  surfaces.  It  is,  therefore, 
conceivable  that  mercurial  stomatitis  may  be  contagious,  as  in  an 
observation  of  Diday,  which  illustrates  in  a  striking  manner  the 
increased  virulence  which  the  buccal  microbes  may  acquire  in  the 
course  of  intoxications. 

Poisons  favor  infection  in  two  principal  ways:  in  some  instances 
they  produce  local  lesions  which  weaken  the  resistance  of  the  tissues 
into  which  the  poisons  are  introduced;  in  other  cases  they  give  rise 
to  general  disturbances  of  the  economy,  which  abolish  its  immunity. 
As  an  example  of  the  former  mechanism,  we  may  cite  the  action  of 
lactic  acid,  which,  when  injected  into  the  muscles  of  a  rabbit,  renders 
this  animal  incapable  of  resisting  symptomatic  anthrax.  Other  sub- 
stances, such  as  acetic  acid,  potassium  acetate,  and  alcohol,  produce 
similar  effects.  Many  antiseptic  substances  act  in  the  same  way. 
Hence,  the  increasing  tendency  to  substitute  asepsis  for  antisepsis 
in  surgical  practice  or  to  utilize  less  energetic  substances,  such  as 
boric  acid. 

In  other  instances  the  process  is  one  of  general  intoxication,  affect- 
ing probably  the  nervous  system.  Thus  Platania  demonstrated  that 
alcohol  and  chloral  favor  the  development  of  anthrax  in  naturally 
immune  animals,  such  as  the  clog,  the  pigeon,  and  the  frog.  Wagner 
verified  the  fact  by  inoculating  anthrax  into  chickens  treated  with 
chloral. 

Influence  of  Autoinfections.  A  last  group  of  poisons  favoring 
invasion  by  bacteria  is  represented  by  substances  which  originate 
within  the  organis;n  itself.  Such  occurs,  for  instance,  in  overworked 
animals ;  the  toxins  produced  under  these  conditions  favor  the  multi- 
plication of  attenuated  viruses  or  the  entrance  of  the  numerous  bac- 
teria normally  inhabiting  the  intestine.  Diabetes  and  glycosuria 
likewise  induce  infection  as  a  result  of  chemical  modifications.  This 
result,  which  has  long  been  recognized  by  chemical  observers,  was 
experimentally  verified  by  Bujwid,  who  injected  sugar  into  inocu- 
lated animals,  and  by  Leo,  who  administered  to  them  phloridzin. 
In  both  instances  infection  was  facilitated  or  rendered  graver. 


ETIOLOQ  V  OF  INFECTIONS. 

Certain  organic  lesions  probably  acl  by  disturbing  the  chemical 
constitution  of  the  organism.  Neumann  demon  trated  that  the 
development  of  the  streptococcus  may  be  favored  by  altering  the 
function  of  the  liver,  by  modifying  the  alkalinity  of  the  blood,  by 

producing  lesions  in  (lie  kidney,  or  by  ligating  the  lower  pari  of  the 
intestine.  In  all  these  cases  there  is  either  excessive  production  of 
toxic  substances  or  insufficienl  elimination. 

Finally,  microbes  create  morbid  dispositions  and  favor  the  devel- 
opment of  secondary  infections  through  the  toxic  substances  which 
they  secrete.  This  fact  will  again  be  referred  to  when  treating  of 
morbid  associations. 

Influence  of  Fasting.  This  influence  was  known  to  the  ancients, 
since  epidemics  following  famines  leave  no  doubl  as  to  their  con- 
nection as  cause  and  effect.  Likewise,  the  frequency  of  infection-. 
from  tuberculosis  to  gangrene,  in  patients  who  cannot  be  nourished, 
is  a  fact  open  to  popular  observation.  The  experiment-  of  Canalis 
and  Morpurgo  demonstrated  the  role  of  starvation  in  this  respect. 
The  resistance  of  the  organism  is  reduced  not  simply  by  suppression 
of  alimentation,  but  also  by  insufficiency  or  bad  quality  of  food. 
The  influence  of  such  conditions  was  well  observed  by  clinician-, 
notably  with  reference  to  tuberculosis.  The  method  of  treatment 
by  overfeeding  consumptives  is  the  opposite  of  the  mentioned  con- 
ditions. Analogous  results  are  observed  in  experimental  medicine. 
I  have  discovered  that  rabbits,  when  abundantly  nourished,  fre- 
quently resist  inoculation  of  variola  pus  or  culture,  while  similar 
animals  receiving  ordinary  rations  succumb  to  this  affection.  This 
observation  led  us  to  nourish  patients  suffering  from  smallpox,  and 
with  satisfactory  results. 

The  results  are  altogether  different  when  we  operate  upon  animals 
which,  after  having  been  subjected  to  a  sufficiently  long  period  of 
starvation,  have  again  been  supplied  with  their  ordinary  food  for 
several  days.1  Under  these  conditions  the  resistance  is  increased  to 
a  remarkable  degree,  at  least  with  regard  to  the  colon  bacillus.  It 
would  not  be  correct  to  generalize  the  results  which  we  have  obtained 
with  the  latter  microbe,  which  is  the  only  one  with  which  we  have 
thus  far  experimented. 

We  starved  five  rabbits  for  five  to  seven  days  and  then  fed  them. 
Three  to  eleven  days  later  we  made  intravenous  injections  of  B. 

1  Roger  et  Josue.  Influence  de  l'inanition  sur  la  resistance  a  rinfection  coliba- 
cillaire.     Soc.  de  biologic,  July  7,  1900. 


94  /  NFEi  TIO  US  DISEASES. 

into  them,  as  well  as  into  control  animals  of  equal  or  greater  weight. 
At  this  time  the  animals  which  had  been  subjected  to  fasting  had 
grown  fat.  but  had  not  yet  recovered  their  former  weight.  Of  these 
five  animals;  only  one  died,  five  days  after  the  inoculation.  Of  the 
five  control  animals,  only  one  survived. 

It  may  be  asked  whether  fasting,  as  prescribed  by  certain  religious 
rites,  is  not  of  greater  hygienic  importance  than  is  believed,  and 
whether  the  modifications  produced  by  fasting  do  not  finally 
strengthen  the  defensive  means  of  the  organism. 

Influence  of  Fatigue  and  Overwork.  The  accidents  following 
excessive  fatigue  have  long  held  the  attention  of  observers.  Fatigue 
diminishes  the  resistance  to  microbic  diseases.  If  it  is  not  permis- 
sible to  believe,  as  did  the  ancient  veterinarians,  that  fatigue  suffices 
of  itself  to  create  glanders  and  anthrax,  it  may  be  admitted  that  it 
favors  or  aggravates  the  development  of  these  maladies.  This  is 
clearly  seen  from  the  interesting  observations  collected  by  Solowieff 
concerning  both  man  and  the  horse.  Clinical  facts,  however,  are  so 
very  complex  that  it  is  impossible  to  define  the  role  of  fatigue.  The 
infectious  diseases  developing  in  army  camps  are  not  altogether  due 
to  the  excessive  work  imposed  upon  the  soldiers.  The  emotions,  the 
privations,  the  crowding,  and  other  bad  hygienic  conditions  must 
also  be  taken  into  account.  We,  therefore,  thought  it  well  to  transfer 
the  question  to  experimental  ground,  and  with  this  end  in  view,  we 
pursued  a  certain  number  of  researches  upon  animals.1 

We  fatigued  various  animals — guinea-pigs,  rabbits,  white  rats, 
cats,  dogs — and  determined  the  influence  of  overwork  upon  the 
results  of  inoculations.  For  this  purpose  we  used  the  anthrax  bacil- 
lus and  the  bacillus  of  symptomatic  anthrax. 

General  fatigue  induced  in  animals  inoculated  either  with  anthrax 
bacillus  or  the  bacillus  of  symptomatic  anthrax  favors  considerably 
the  development  and  generalization  of  infections.  The  overworked 
animals  invariably  died  before  those  left  at  rest.  Quite  often  they 
succumbed  while  the  latter  resisted.  It  must  be  noted  that  animals 
of  the  same  size  and  submitted  to  the  same  exercises  by  no  means 
possess  the  same  morbid  aptitude.  Some  resist  better  than  others, 
but  these  individual  variations  are  observed  in  all  experiments  and 
in  nowise  modify  the  meaning  of  the  results  which  we  have  obtained. 

If  general,  fatigue  explains  the  development  of  infections,  the  over- 

1  Charrin  et  Roger.  Contribution  a  l'6tude  experimentale  du  surmenage.  Son 
influence  sur  l'infection.    Arch,  de  physiol.,  Feb.  19,  1890. 


ETIOLOQ  v  OF  INFECTIONS. 

work  imposed  upon  an  organ  may  account  for  certain  clinical  forms. 
Cerebral  rheumatism,  for  Instance,  occurs  only  in  individuals  ad- 
dicted to  intellectual  activity,  or  in  those  whose  tiervou  system  has 
suffered  from  late  hours,  dissipation,  ambition,  and  disappointment. 
Likewise,  in  young  subjects,  growing  bonei  are  predisposed  to 
microbie  localizations,  ,-is  expressed  by  i In-  developmenl  <<\  o 
myelitis.  Conversely,  an  inactive  organ  does  noi  offer  a  -oil  for  the 
localization  of  microbes.  Children  suffering  from  mumps  do  not 
develop  orchitis;  this  localization  does  not  occur  until  after  pub) 

Development  of   Epidemics;    Their  Variations  with   Countries 
and  Epochs.    The  facts  above  reported  lend  to  the  conclusion  thai 
in  all  infections  two  factors  are  to  be  taken  into  consideration :     I 
an  external  factor,  the  pathogenic  microbe;  (2)  an  internal  factor, 
the  state  of  the  organism. 

The  pathogenic  microbe  comes  from  without.  It  was  primarily 
a  simple  saprophyte,  which  accidentally  settled  in  a  living  being,  its 
special  organization  enabling  it  to  accommodate  itself  to  the  new- 
medium.  It  thus  loses  its  ability  to  thrive  outside  living  organism-, 
and  acquires  new  qualities  varying  so  greatly  from  the  original  that 
it  is  impossible  to  refer  the  isolated  pathogenic  microbe  to  the  sapro- 
phytic species  from  which  it  evolved. 

After  the  microbe  has  once  acquired  virulent  properties  it  does 
not  remain  immutable.  On  the  contrary,  it  is  modified  by  various 
circumstances,  its  virulence  increases  or  diminishes,  and  it  acquires 
a  special  aptitude  to  vegetate  in  certain  tissues  rather  than  in  others. 
The  evolution  of  pathogenic  microbes  through  the  ages  and  countries 
thus  leads  us  to  admit  that  the  clinical  types  also  cannot  remain 
immutable.  It  is  conceivable  that  new  infections  may  appear  under 
the  influence  of  cosmic  and  many  other  fortuitous  agencies,  and  that 
affections  of  ancient  origin  may  be  modified  or  disappear. 

In  view  of  the  fact  that  epidemics  are  at  times  suddenly  revived 
and  reigning  infections  assume  unusual  gravity  or  exceptional  mild- 
ness, it  must  be  admitted  that  infectious  agents  may  become  sud- 
denly more  or  less  virulent  under  the  influence  of  changing  atmo- 
spheric conditions.  It  is  more  likely,  however,  that  the  various 
cosmic  changes  act  with  greater  energy  upon  the  invaded  organisms 
than  upon  the  invaders.  As  has  already  been  stated,  the  more 
highly  developed  and  delicate  the  animal  organization,  the  more  sen- 
sitive it  is  to  variations  in  the  surrounding  medium.  For  instance, 
man  is  influenced  by  changes  in  atmospheric  pressure  or  thermal 


96  INFECTIO  US  DISEASES. 

variations,  far  more  than  the  microbe.  The  explanation  of  "genie 
epidemique "  must,  therefore,  be  sought  in  the  disturbances  mani- 
fested in  massed  humanity.  The  appearance,  course,  more  or  less 
extensive  ravages,  and  decline  or  disappearance  of  epidemics  depend 
chiefly  upon  the  influence  exerted  by  meteoric,  hygienic,  and  social 
conditions  upon  human  organisms. 

The  insufficiency  and  laconicism  of  ancient  descriptions  make  it 
difficult  to  compare  the  diseases  of  the  present  time  with  those  of 
the  past.  With  reference  to  some  of  them,  however,  the  course  of 
evolution  is  not  a  matter  of  doubt.  For  instance,  leprosy  was  very 
frequent  in  the  thirteenth  century,  when  there  were  2000  leprosy 
houses  in  France  and  19,000  in  Europe.  At  present  this  disease  is 
localized  in  a  few  regions.  In  France  sporadic  cases  are  met  with 
around  Marseilles  and  Nice. 

On  the  other  hand,  some  diseases  have  made  their  appearance  at 
a  certain  epoch,  and  do  not  seem  to  be  destined  to  disappear  in  the 
near  future.  For  example,  the  eruptive  fevers  were  imparted  in  the 
sixth  century.  Although  smallpox  existed  in  China  a  thousand 
years  before  Christ,  its  occurrence  in  Europe  was  not  mentioned  until 
the  year  570  a.d.  by  Marius,  bishop  of  Avenches  (Switzerland),  and 
in  580  a.d.  by  Gregory  of  Tours.  Measles,  which  dates  from  the 
same  epoch,  seems  to  have  definitely  settled  among  us.  Scarlet 
fever  was  mentioned  by  Ingrassias  in  the 'sixteenth  century.  Finally, 
sudor  anglicus  appeared  in  England  for  the  first  time  in  the  fifteenth 
century  and  ceased  in  1551.  The  symptoms  of  the  first  epidemics, 
however,  were  very  different  from  those  presented  by  modern  epi- 
demics, the  history  of  which  begins  in  the  eighteenth  century  (suette 
picarde,  1718-23).  Therefore,  some  authorities,  such  as  Hecker  and 
Littre,  have  denied  the  identity  of  the  two  epidemics. 

Passing  to  modern  times,  we  find  cerebrospinal  meningitis,  which 
did  not  appear  until  the  nineteenth  century.  In  1831  cholera  made 
its  first  appearance  in  Europe,  and  the  following  year  it  entered 
France.  Since  that  epoch  it  has  returned  several  times,  always  pre- 
serving the  same  clinical  characters,  but  tending  more  and  more  to 
acclimate  itself  to  our  countries  and  to  become  localized  in  small 
endemic  foci. 

The  symptomatology  of  infectious  diseases  has  not  remained  inva- 
riable. The  history  of  influenza  reveals  that  the  malady  was  for- 
merly observed  in  the  form  of  catarrhs  and  pulmonary  localizations. 
At  present  it  occurs  also  with  nervous  symptoms  which,  in  some 


ETIOLOQ  ?  OF  INFECTIONS.  !>7 

cases,  are  the  predominant  or  only  manifestation  ,  and  an 
For  months  after  apparent  recovery.    Similar  remark   are  appli< 
to  pneumonia.    This  infection  no  longer  presente  the  former  fn 
plain  character,     lis  resolution  is  far  more  tedious,  and  everal 
after  defervescence  stetlioscopic  signs  may  be  found  which  embi 
the  physician  and  lead  him  to  doubl  the  nature  of  the  pro© 

The  causes  of  all  these  changes  are  mostly  unknown.  A  few  con- 
ditions, however,  have  been  determined. 

At  nil  times  it  has  been  noted  thai  fatal  epidemics  were  preceded 
by  cosmic  perturbations,  greal  variations  in  pressure  and  tempera- 
ture, earthquakes,  and  volcanic  eruptions.  At  the  presenl  time  we 
are  unable  to  conceive  the  mode  of  action  of  these  cosmic  agencies. 

We  are  a  little  better  acquainted  with  the  influence  of  social  con- 
ditions. Infectious  diseases  change  in  frequency  and  form  parallel 
to  variations  in  the  progress  of  civilization.  During  the  warlike 
periods  of  humanity  infections  reigned  as  a  result  of  traumatism, 
overwork,  and  crowding.  During  the  periods  of  naval  conquests 
we  transported  beyond  the  seas  the  maladies  of  our  continent  and 
imported  various  exotic  infections. 

Modern  civilization  has  arrested  the  course  of  epidemics,  and  the 
advances  of  therapeutics  have  diminished  their  mortality.  Vaccina- 
tions tend  to  abolish  certain  diseases,  notably  variola. 

Some  infections,  however,  persist  with  obstinate  tenacity.  Tuber- 
culosis seems  to  be  on  the  increase. 

Although  hygiene  has  diminished  the  frequency  of  infections,  it 
has  been  less  effective  as  regards  intoxications.  The  latter  become 
more  and  more  numerous.  Alcoholism  tends  to  favor  certain  infec- 
tions and  to  modify  clinical  types.  The  advances  of  civilization  as 
a  cause  of  growing  excitation  of  the  nervous  system  favor  the  devel- 
opment of  cerebral  manifestations,  thus  modifying  clinical  types. 
The  pathology  of  the  nineteenth  century  differs  from  that  of  pre- 
ceding ages  and  will  differ  from  that  of  the  future.  Infections  are 
subject  to  the  general  laws  of  evolution,  and,  while  we  are  unable  to 
comprehend  all  the  conditions  which  contribute  to  modify  the  clinical 
characters  of  diseases,  we  at  least  understand  that  they  cannot 
remain  immutable. 


CHAPTER  IV. 

PATHOGENESIS  OF  INFECTIONS. 

Role  of  Microbes  in  the  Development  of  Infections.  Importance  of  the  Number.  Vari- 
ations of  Virulence.  Exaltation  and  Attenuation.  Selective  Harmfulness  for 
Certain  Organs  or  Tissues.  Modes  of  Entrance  of  Microbes.  Importance  of  the 
Mode  of  Entrance  with  Regard  to  Gravity  and  Symptoms  of  Infection.  Modes  of 
Action  of  Microbes.  Discussion  of  Hypotheses.  Role  of  Microbic  Poisons.  Study 
of  Putrefaction  Poisons  and  Gastrointestinal  Poisons.  Autointoxications  of  Gastro- 
intestinal Origin.  Toxins  of  Pathogenic  Microbes.  Local  Action  and  General 
Manifestations  Ascribable  to  These  Toxins.  Study  of  the  Principal  Toxins  Produced 
by  Pathogenic  Microbes.  The  Poisons  in  the  Infected  Organism.  Toxic  Charac- 
ter of  the  Blood,  Serum,  and  Urine.     Urinary  Toxins  and  Ptomains. 

Role  of  Microbes  in  the  Development  of  Infections;  Role  of 
Number.  An  infectious  disease  expresses  the  struggle  engaged 
between  an  animal  organism  and  a  microbic  agent.  In  order  to 
understand  the  evolution  of  the  disease  we  must  study  successively 
those  modifications  of  the  organism  and  of  the  microbe  which  favor 
or  hinder  the  production  of  morbid  phenomena. 

Let  us  first  consider  the  role  of  the  microbe.  It  is  now  known  that 
it  is  necessary  to  take  into  account  both  the  quantity  and  the  quality 
of  pathogenic  agents  attacking  the  organism. 

In  the  beginning  of  bacteriological  studies,  when  an  endeavor  was 
made  to  differentiate  infections  from  intoxications,  it  was  thought 
that,  contrary  to  what  is  true  with  regard  to  poisons,  quantity  was 
of  no  importance  when  the  question  was  one  of  microbic  virus.  This 
was  at  the  time  when  Davaine  showed  that  one-millionth  of  a  drop 
of  blood  derived  from  an  animal  infected  with  anthrax  possesses 
sufficient  virulence  to  cause  death.  The  researches  of  Chauveau, 
W.  Cheyne,  and  Bouchard  have  fully  established  the  importance  of 
quantity.  Thus  the  guinea-pig,  of  all  animals  the  most  susceptible 
to  tuberculosis,  does  not  contract  the  infection  unless  eight  hundred 
and  twenty  bacilli  are  introduced  beneath  its  skin.  With  pus  cocci 
far  greater  numbers  are  requisite. 

Operating  with  proteus  vulgaris,  Watson  Cheyne  discovered  that 
6,000,000  of  microbes  injected  beneath  the  skin  do  not  produce  any 
lesion;  8,000,000  cause  the  formation  of  an  abscess;  56,000,000  give 


I'A  TH0QENESI8  OF  INFECTIONS. 

rise  to  a  phlegmon  to  which  the  animal  3uccum.bc  within  fi 
weeks;  225,000,000  must  be  injected  in  order  to  cau  e  death  within 
twenty-four  or  thirty  hours.     Experimenting  with  staphylocoi 
upon  rabbits,  he  found  thai  250,000,000  microbes  are  required  to 
produce  an  abscess  and  to  cause  death,  one  milliard  (1,000,000,000  , 

We  have  obtained  quite  similar  results  by  inoculating  into  guinea- 
pigs  cultures  of  staphylococcus  aureus  obtained  from  a  phlegmon 
consecutive  to  erysipelas.  An  injection  of  0.2c.cm.  produced  a  cir- 
cumscribed abscess;  ().(>  cciii.  caused  edema,  followed  by  a  patch  of 
sphacelus;  with  exfoliation  of  the  slough  the  connective  tissue  and 
subjacent  muscles  were  found  to  be  necrotic.  Finally,  with  1  c.cm. 
an  enormous  invading  edema  was  obtained  which  ended  fatally  in 
four  or  five  days. 

These  facts  are  interesting  because  they  show  that  inoculation  of 
the  same  microbic  cultures  into  the  same  region  in  animals  of  the  same 
species  gives  rise  to  manifestations  which  vary  in  gravity  and  nature 
according  to  the  dosage.  The  experimenter  is  thus  able  to  produce, 
at  will,  abscess,  gangrene,  or  fatal  edema. 

In  all  these  experiments  the  microbes  were  injected  beneath  the 
skin.  By  varying  the  mode  of  introduction,  different  results  are 
obtained.  To  produce  suppuration  with  staphylococcus  aureus  it 
was  necessary  in  the  researches  of  Herman  to  inject  4  c.cm.  to  5  c.cm. 
of  the  culture  into  the  peritoneal  cavity,  0.75  c.cm.  to  1  c.cm.  beneath 
the  skin,  0.25  c.cm.  into  the  pleural  cavity  or  arachnoid  space, 
0.5  c.cm.  into  the  veins,  and  0.0001  c.cm.  into  the  anterior  chamber 
of  the  eye.  The  anterior  chamber  of  the  eye,  therefore,  is  the  most 
poorly  protected  part  of  the  organism.  The  same  is  also  demon- 
strated by  the  study  of  symptomatic  anthrax.  This  virus,  which  is 
inoffensive  to  rabbits  when  injected  hypodermically,  causes  speedy 
death  when  introduced  into  the  anterior  chamber  of  the  eye. 

Variations  in  the  Virulence  of  Microbes.  A  fact  of  prime  importance 
dominates  the  history  of  all  infections,  viz.,  the  virulence  of  microbes 
is  not  fixed  and  unchangeable.  It  is  modified  by  a  vast  number  of 
circumstances  of  which  several  have  been  clearly  determined. 

As  exaltation  may  be  considered  an  adaptation  to  new  biological 
conditions,  it  is  conceivable  that  a  microbe  can  be  habituated  to  the 
living  medium  and  develop  more  and  more  easily  therein.  Inocula- 
tions in  series  offer  the  best  means  of  increasing  pathogenic  potency. 
On  the  other  hand,  cultivation  in  inert  media  is  the  surest  method 
for  diminishing  pathogenic  potency,  and  the  more  the  culture  medium 


100  INFECTIOUS  DISEASES. 

differs  from  the  organic  medium  the  more  speedily  is  the  virus 
attenuated.  This  weakening  is  more  rapidly  effected  in  mineral 
solutions  than  in  bouillon,  and  more  readily  in  bouillon  than  in 
blood  serum  or  in  defibrinated  blood. 

It  is  to  be  noted  that  a  microbe  exalted  for  one  animal  species  is 
not  necessarily  so  for  others.  We  have  studied  a  specimen  of  anthrax 
which,  after  successive  passages  through  rabbits,  had  become,  con- 
trary to  the  rule,  far  more  virulent  for  this  animal  than  for  the 
guinea-pig.  In  this  connection  we  may  cite  the  experiments  of 
Pasteur,  showing  that  the  virus  of  hydrophobia  is  attenuated  when 
inoculated  into  monkeys,  as  is  evident  from  the  increase  in  the  period 
of  incubation. 

These  results  are  not  merely  of  theoretical  interest.  They  explain 
certain  facts  which,  at  first,  may  seem  incomprehensible. 

In  fact,  under  the  habitual  conditions  of  life,  we  see  that  viruses, 
by  passage  through  the  organisms  of  different  animals,  undergo  such 
modifications  as  to  puzzle  the  observer  as  to  their  origin.  Thus,  it 
is  now  demonstrated  that  tuberculosis  is  produced  in  all  animals  by 
a  single  bacillary  species.  The  microbes  have  suffered  changes,  how- 
ever, according  as  they  have  invaded  mammalia  or  birds,  thus  con- 
stituting two  varieties  which  have  appeared  to  some  observers  as 
two  different  species.  The  bacillus  exalted  for  birds  is  attenuated 
for  mammalia,  and  vice  versa. 

The  knowledge  of  these  facts  shows  that  inoculation  into  animals 
does  not  always  yield  results  responding  to  the  previsions  of  clinical 
observation.  We  cannot  establish  a  diagnosis  for  man  upon  experi- 
mental results.  Virulence  being  a  contingent  property,  depending 
rather  upon  the  invaded  organism,  it  is  conceivable  that  it  should 
differ  with  each  being  under  consideration. 

Selective  Injuriousness  of  Pathogenic  Agents.  Some  of  the  patho- 
genic agents  manifest  an  affinity  for  a  certain  organ  or  tissue  in  which 
they  settle,  and  manifest  no  tendency  to  invade  other  parts.  They 
are  even  incapable,  at  times,  of  emigrating  from  the  organic  territory 
to  which  they  are  habituated.  Thus  the  microbe  of  mumps  fixes 
itself  in  certain  glands;  the  cholera  vibrio  multiplies  exclusively  in 
the  intestine ;  the  agent  of  hydrophobia  invades  the  nervous  system. 
Some  specific  bacteria,  however,  are  apt  to  colonize  more  or  less 
everywhere.  Such,  for  instance,  are  the  bacillus  of  glanders,  the 
tubercle  bacillus,  and  the  agent  of  syphilis. 

On  the  other  hand,  the  non-specific  bacteria  are  all  capable  of 


PATHOGENESIS  OF  INFECTIONS.  ]ol 

developing  in  the  most  dissimilar  pari    of  the  organism.    There  is 

no  tissue  or  ;in  organ  which  cannot  be  invaded  by  i  lie  staphylococ 
streptococcus,  pneumococcus,  or  colon  bacillu  . 

Even  these  common  agents,  however,  are  in  some  degree  capable 
of  education,  and  acquire  a  special  aptitude  to  live  in  :i  certain  ti 
They  become  used  to  the  biological  conditions  of  thai  pari  of  the 
organism,  and  no  longer  manifest  any  inclination  to  invade  others. 
This  fact  was  illustrated  in  a  case  of  acute  ascending  paralysis  which 
i In-  author  studied  with  Dr.  .Io-imV     The  manifestations  were  due 
to  a  pneumococcus  which,  when  inoculated  into  animals,  prod 
spinal  symptoms.    This  microbe,  then,  behaved  as  if  it  bad  acquired 
a  sort  of  selective  harmfulness  for  the  nervous  tissues  by  virl 
its  first  passage  through  the  spinal  cord  of  our  patient. 

Our  idea  was  taken  up  and  developed  by  Drs.  Bezancon  and 
Labbe,2  who  collected  a  certain  number  of  facts  showing  thai 
microbes  obtained  from  an  organic  lesion  when  introduced  into 
animals  localize  themselves  in  that  part  which  was  attacked  in 
the  human  subject.  Thus,  Dreschfeld  produced  endocarditis  in 
rabbits  which  were  inoculated  with  a  streptococcus  derived  from 
an  infectious  endocarditis. 

These  facts  prove  that  microbes  may  acquire  the  habit  of  colon- 
izing in  a  certain  organ  or  tissue  in  preference  to  others.  It  may 
now  be  asked  why  a  microbe,  for  the  first  time,  localizes  itself  at  a 
certain  point  of  the  economy.  Several  conditions  may  intervene. 
One  of  these  is  the  mode  of  entrance  of  the  pathogenic  agent. 

Modes  of  Entrance  of  Infectious  Agents.  Certain  microbes 
possess  such  a  high  degree  of  virulence  that  their  introduction  into 
the  organism  is  invariably  followed  by  the  development  of  a  fatal 
disease.  No  matter  what  the  mode  of  introduction  may  be,  the 
result  is  the  same.  Such,  for  instance,  is  the  case  observed  when 
chicken  cholera  is  inoculated  into  the  rabbit.  This  fact,  however,  is 
exceptional.  In  most  cases  infection  is  modified  according  to  the 
channel  by  which  the  virus  enters. 

The  usual  modes  of  entrance  of  morbific  germs  are  four:  the  skin 
and  the  subcutaneous  cellular  tissue,  the  respiratory  passages,  the 
alimentary  canal,  and  the  genito-urinary  apparatus. 

1  Roger  et  Josue.  Un  cas  de  paralysie  ascendaute  aigue.  Presse  medicals.  Ju  2  i 
1898. 

2  Bezancon  and  Labbe.     Role  de  l'aecutumance   dan?  la  determination  des  lex 
lions  microbiennes.     Presse  meclieale.  March  7.  1900. 


102  INFECTIOUS  DISEASES. 

Infections  of  Cutaneous  Origin.  In  this  connection,  the  first  ques- 
tion to  be  asked  is  whether  pathogenic  agents  are  capable  of  invading 
the  organism  through  the  unbroken  skin.  As  a  rule,  they  are  not. 
The  rule  is  not,  however,  without  exceptions,  especially  as  regards 
the  mucous  membranes.     Let  us  first  see  what  occurs  with  the  skin. 

Ancient  observers  admitted  that  viruses  could  penetrate  through 
the  intact  epidermis.  The  fact  seems  to  be  real  with  regard  to 
certain  pus  cocci,  as  is  demonstrated  by  the  frequencjr  of  small 
pustules  upon  the  back  of  the  hands  of  anatomists.  The  microbes 
are  undoubtedly  introduced  through  the  sebaceous  glands.  Roth, 
by  rubbing  the  skin  of  guinea-pigs  with  a  mixture  of  fat  and  a 
bacteria  culture,  was  able  to  produce  abscesses.  When  experimenting 
with  anthrax  he  witnessed  the  production  of  a  local  edema  which 
in  some  cases  proved  fatal.  No  result,  howrever,  was  seen  when  the 
culture  was  simply  deposited  upon  the  skin  without  any  friction. 
By  similar  procedures,  Babes  succeeded  in  inoculating  glanders  into 
guinea-pigs  through  the  healthy  skin. 

When  infection  occurs  in  the  skin  the  lesion  often  remains  limited 
to  the  spot.  This  is  what  happened  in  Roth's  experiments  with 
the  anthrax  bacillus.  The  same  is  demonstrated  by  clinical  obser- 
vation. Lupus  and  anatomical  tubercles  manifest  hardly  any  ten- 
dency to  generalization.  The  fact  may  be  due  to  the  special  struc- 
ture of  the  skin.  It  may  also  be  explained  by  the  temperature  of 
the  skin,  which  is  too  low  to  favor  active  vegetation  of  the  microbic 
agent. 

Subcutaneous  Inoculations.  In  most  cases  the  virus  is  deposited 
beneath  the  skm,  either  in  the  cellular  tissue,  or  even  more  deeply 
in  the  muscles  and  nerves. 

With  the  same  virus  the  results  may  differ  according  to  the  point 
of  subcutaneous  inoculation.  Thus  the  regions  where  the  connective 
tissue  is  dense  are  not  very  favorable  for  the  propagation  of  microbes. 
If  a  very  energetic  virus,  such  as  that  of  symptomatic  anthrax  or  of 
gaseous  gangrene,  is  inoculated  into  the  tip  of  the  tail  or  the  ear, 
only  a  local  lesion  capable  of  causing  the  loss  of  a  part  of  the  organ 
results,  but  ending  in  recovery.  The  density  of  the  cellular  tissue 
and  the  low  temperature  of  the  region  hinder  the  vegetation  of  the 
microbes  and  insure  survival  of  the  animal,  which  would  certainly 
perish  if  the  inoculation  were  practised  at  some  other  point. 

The  results  of  inoculation  also  vary  according  to  the  depth  of  the 
wound.     In  this  respect  nothing  is  more  interesting  than  the  study 


PA  THOQENESIS  OF  INFECTIONS. 

of  hydrophobia.     Helman  discovered  thai  the  adipoa  offers 

an  unfavorable  channel  of  absorption  for  the  hydrophobic  virus. 
Fat  dogs,  therefore,  resist  hypodermic  inoculation,  while  the  young 
and  thin  ones  mostly  perish.  When  thevirusu  introduced  into  the 
subcutaneous  cellular  tissue  of  mbbiis,  7o  per  ceni .  of  the  inoculated 
animals  die.  If  the  injection  is  made  into  a  muscle,  the  mortality 
rises  to  <s>r)  per  cent.  If  sectioned  musHe-  are  operated  upon,  and 
the  virus  is  introduced  between  the  muscular  fibres,  all  the  animals 
succumb. 

The  deductions  which  may  be  drawn  from  these  experiments  are 
.self-evident.  The  great  danger  attending  deep  wounds  is  in  part 
due  to  the  introduction  of  the  virus  into  the  subcutaneous  mu 
and  nerve  fibres.  Numerous  experiments  have  shown  that  the 
hydrophobia  virus  follows  the  nerve  fibres  in  order  to  reach  the 
nerve  centres,  where  its  localization  gives  rise  to  clinical  mai 
tations  of  the  most  fearful  character.  Hence  the  more  richly  the 
wounded  part  is  supplied  with  nerves  the  more  certain  is  contam- 
ination and  the  shorter  the  period  of  incubation. 

Infections  through  the  Mucous  Membranes.  The  mucous  membranes 
are  more  easily  penetrated  by  microbes  than  the  skin.  The  patho- 
genic agents  often  leave  no  trace  of  their  passage  or,  after  giving 
rise  to  some  slight  and  curable  lesion,  invade  the  neighboring 
lymphatic  ganglia.  By  depositing  tuberculous  sputum  in  the  lower 
conjunctival  cul-de-sac,  without  any  traumatism  of  the  mucous 
membrane,  Cornet  observed  no  more  than  a  little  redness  at  the 
point  of  inoculation.  The  cervical  glands,  however,  became  caseated, 
and  microscopic  examination  revealed  in  them  the  presence  of 
numerous  tubercle  bacilli.  He  operated  upon  the  mucous  mem- 
branes of  the  nose,  gums,  penis,  and  vagina  with  similar  results. 

Infection  through  the  Respiratory  Passages.  The  respiratory  tract 
is  believed  to  be  a  frequent  channel  of  contamination.  Many  authors 
assert  that  the  germs  of  eruptive  fevers,  especially  those  of  measles 
and  variola,  are  introduced  by  this  route. 

On  the  other  hand,  it  has  been  remarked  that  while  infection  is 
grave  when  it  occurs  spontaneously,  it  is  generally  mild  when  it 
originates  by  subcutaneous  inoculation.  This  is  demonstrated  by 
the  practice  of  variolization. 

In  studying  the  respiratory  mode  of  entrance,  authors  have  ck  - 
particularly  the  bacillus  anthracis.   Flugge  and  Wyssokowicz  asserted 
that  the  bacillus  could   not  pass  through  the  intact  lung.      Such 


104  INFECTIOUS  DISEASES. 

conclusion  can  no  longer  be  accepted  in  view  of  the  researches  of 
Buchner.  Muskalbluth,  and  Enderlein.  These  authors  made  numerous 
experiments,  consisting  in  the  injection  of  the  virus  directly  into  the 
trachea,  or  in- causing  it  to  be  breathed  in  the  shape  of  dried  powder. 
Most  of  the  animals — rats  and  guinea-pigs — died. 

Buchner  produced  a  general  infection,  without  any  pulmonary 
alteration,  by  causing  animals  to  inhale  anthrax  spores.  By  employ- 
ing the  bacilli  themselves  he  often  observed  red  hepatization  and, 
in  these  cases,  the  animals  survived.  This  result  is  explained  by  the 
fact  that  the  adult  microbes,  which  are  comparatively  weak,  succumb 
and  transude  an  irritating  substance,  while  the  spores  give  birth  to 
vigorous  bacilli  of  great  resistance.  The  local  lesion  is,  therefore, 
the  result  of  the  organic  resistance,  though  this  is  not  always  suffi- 
cient to  prevent  infection.  This  is  further  illustrated  by  the  study 
of  the  pneumococcus.  If  this  microbe  is  introduced  into  the  trachea 
of  an  animal  very  sensitive  to  its  action,  such  as  the  rat  or  the  rabbit, 
no  pulmonary  lesion  is  obtained,  but  death  supervenes  as  the  result 
of  a  general  infection — that  is,  a  veritable  septicemia.  If  a  more 
resistant  animal  is  experimented  upon,  the  dog,  for  instance,  the 
result  is  a  fibrinous  pneumonia.  The  same  is  true  with  regard  to 
man.  The  pneumococcus  is  present  in  the  oral  cavity  of  many 
healthy  persons.  When  a  disturbing  influence  diminishes  the  or- 
ganic resistance  a  pneumonia  is  produced  expressing  the  reaction 
of  the  individual  against  the  pathogenic  agent.  The  same  remark 
is  also  applicable  to  diphtheria. 

In  the  majority  of  cases  the  bacilli  of  tuberculosis  invade  the  organ- 
ism through  the  respiratory  organs.  The  experiments  of  Tappeiner 
demonstrate  that  dogs,  which  are  quite  resistant  to  tuberculosis, 
easily  contract  this  malady  when  they  inhale  dried  and  pulverized 
sputa.  The  local  lesion,  however,  may  be  lacking  or  promptly 
repaired.  The  bacilli  pass  through  the  lung  without  leaving  any 
lasting  trace  of  their  passage,  and  take  up  their  abode  in  other  parts 
of  the  organism.  They  may  cause  a  general  infection  or  be  arrested 
in  the  mediastinal  ganglia.  The  latter  event  is  frequently  observed 
in  children  who  are  so  often  victims  of  seemingty  primary  tracheo- 
bronchial adenopathies. 

It  is  not  to  be  assumed,  however,  that  the  respiratory  passages 
represent  a  door  open  to  all  infections.  The  bacilli  of  symptomatic 
anthrax  and  of  gaseous  gangrene  may  be  introduced  into  the  trachea 
with  impunity.     They  give  rise  to  no  disturbance,  for  the  reason, 


PATHOGENESIS  OF  INFECTIONS.  106 

perhaps,  that  these  agents  are  anaerobic,  [t  must  further  be  remem- 
bered that  in  this  organ,  as  id  the  rest  of  the  economy  .  important 
means  of  defense,  including  phagocytosis,  exi  t. 

Infection  by   the   Alimentary   Canal.       Under  QOrmal   eondition-   the 

digestive  tract  contains  a  prodigious  quantity  of  microbes,  of  which 
several  are  pathogenic.  Owing,  however,  to  the  numerous  modes  of 
protection  with  which  this  canal  is  endowed,  the  presence  of  the 
microbes  gives  rise  to  no  disturbance.  Neverl  heless,  infection  is  pos- 
sible, though  here  it  is  more  didieiili  than  through  the  respiri 
passages.  While  the  inhalation  of  the  bacillus  anthracis  kills  most 
of  the  animals — rats  or  guinea-pigs— its  ingestion  is,  as  a  rule,  well 
resisted. 

The  alimentary  canal  may  be  the  starting  point  of  a  great  num- 
ber of  infectious  diseases.  It  will  suffice  to  mention  typhoid  fever, 
dysentery,  and  cholera. 

Tuberculous  lesions  are  also  frequently  observed  in  the  digestive 
canal  and  are  generally  secondary  to  deglutition  of  sputa.  They 
may,  however,  be  primary,  as  a  result  of  ingestion  of  contaminated 
food  and,  particularly,  milk  drawn  from  cows  affected  with  mam- 
mary tuberculosis. 

Tuberculosis  of  intestinal  origin  may  appear  in  two  different  forms: 
1.  The  localizations  are  sometimes  found  in  the  canal  and  the  mode 
of  entrance  is  readily  recognized.  2.  At  other  times  no  intestinal 
lesion  is  discoverable,  since  the  bacilli  have  passed  onward  to  colonize 
in  the  mesenteric  ganglia,  peritoneum,  or  even  the  lungs. 

Of  all  the  microbes  normally  inhabiting  the  intestine  the  most 
interesting  is  undoubtedly  the  bacillus  coli  communis.  The  study 
of  the  diseases  which  it  is  capable  of  producing  is  the  finest  illustra- 
tion of  the  surprising  modifications  undergone  by  a  microbe.  An 
innocent  guest  in  most  human  subjects,  under  influences  as  yet 
vaguely  recognized,  it  may  acquire  noxious  properties  and  give  rise 
to  the  most  varied  intestinal  disturbances — simple  diarrhea,  dysen- 
teriform  diarrhea,  or  some  form  of  cholera.  It  may  even  leave  the 
intestine  and  produce  either  septicemias  or  bronchopneumonias:  or, 
by  ascending  the  biliary  passages,  induce  a  suppurating  angiocholitis. 

Migration  may  occur  when  there  is  some  obstacle  to  the  course  of 
fecal  matters.  Artificial  occlusion  of  the  rectum  suffices  to  cause 
bacteria  to  pass  into  the  general  circulation  (Possner  and  Lewim. 
The  same  phenomenon  is  observed  in  the  course  of  certain  infections 
and  intoxications.     According  to  Chvostek  and  Egger,  after  a  mala- 


106  INFECTIOUS  DISEASES. 

rial  paroxysm  and  after  the  injection  of  tuberculin,  various  microbes 
can  be  found  in  the  urine,  particularly  the  colon  bacillus,  which 
probably  comes  from  the  intestine.  The  researches  of  Beco,  Wurtz, 
and  Hudelo  demonstrate  that  poisoning  by  tartar  emetic,  canthari- 
din  or  alcohol  likewise  favors  penetration  of  bacilli.  Authors  have 
thus  been  led  to  attribute  to  infection  a  role  in  the  origin  of  alcoholic 
cirrhosis. 

Infection  by  the  Genito-urinary  Organs.  Under  normal  conditions 
microbes  do  not  pass  beyond  the  navicular  fossa.  They  may  often, 
however,  invade  the  rest  of  the  urethra  after  catheterization  or  after 
sexual  intercourse.  In  the  latter  instance,  several  infections  may 
be  transmitted,  from  gonorrhea  to  tuberculosis.  The  infection  may 
pass  from  the  urethra  into  the  bladder,  but  scarcely  ever  beyond 
that  point.  As  has  been  established  by  Albarran  and  Halle,  nu- 
merous microbes  are  very  frequently  found  in  the  bladder.  Only 
one,  however,  the  bacillus  coli,  is  capable  of  advancing  to  the  renal 
pelvis  and  kidneys.  It  is  interesting  to  note  that  this  microbe 
manifests  the  same  tendency  to  ascend  to  the  liver  along  the  excre- 
tory passages  and  contrary  to  the  current  of  the  bile.  Angiocholitis 
and  suppurative  nephritis  represent  two  perfectly  analogous  pro- 
cesses. 

In  women  protection  against  microbes  is  quite  efficacious.    Even 
after  parturition,  infections  of  genital  origin  are  difficult.     Experi- 
ments have  shown  that  the  uterus  of  a  puerperal  woman  possesses 
a  special  resistance.     Certain  microbes,  however,  notably  the  strep- 
tococcus, can  invade  it,  producing  one  of  the  forms  of  puerperal  fever. 

Infection  by  the  Organs  of  Sense,  Serous  Membranes,  and  the  Nervous 
System.  It  has  ahead}''  been  stated  that  the  conjunctiva  may 
serve  as  a  channel  of  entrance,  but  the  anterior  chamber  especially 
offers  an  important  route  of  introduction,  at  least  from  an  experi- 
mental standpoint.  Thus,  for  instance,  hydrophobia  as  surely  de- 
velops when  the  virus  is  deposited  at  this  point  as  when  it  is  intro- 
duced into  the  nervous  system.  Cohnheim  and  Baumgarten  have 
discovered  that  this  is  a  very  certain  channel  for  the  introduction 
of  tuberculosis. 

The  serous  membranes  are  not  a  route  habitually  open  to  infec- 
tions, except  in  cases  of  traumatism.  Experimenters  frequently 
employ  it  for  the  introduction  of  microbes.  At  all  events,  the  results 
are  similar  to  those  obtained  with  inoculations  into  the  mucous 
membranes.     In  some  instances  the  animal  resists ;  in  others  a  gen- 


PATHOGENESIS  OF  INFECTIONS.  ]07 

era!  infection  is  prod  need  without  any  lesion  al  the  poinl  of  injection. 
At  oilier  limes  a  local  lesion  is  caused  which  may  or  may  nol  be 
followed  by  general  infection. 

Lastly,  another  channel  for  contamination  is  the  nerv<  tern. 

The  agent  of  hydrophobia  propagates  through  the  nei   i  both 

clinical  observation  and  experimental  researches  have  demonstrated. 
In  this  way  the  virus  reaches  the  nerve  centres.  It  is  conceivable, 
therefore,  that  the  nearer  the  affected  nerve  U  to  the  spinal  bulb 
the  shorter  the  period  of  incubation,  and,  furthermore,  the  firsl  mani- 
festations will  vary  with  the  region  primarily  contaminated. 

Infection  by  the  Vascular  System.      Whatever  the   route  by  which 

microbes  arc  introduced  into  the  organism,  they  either  remain  al 
the  point  where  they  are  primarily  deposited  or  invade  the  organism. 
In  the  former  case  they  may  be  speedily  destroyed  or  give  rise  to 
the  formation  of  a  local  lesion,  which  often  represents  a  means  of 
defense  opposed  by  the  organism.  However,  the  microbes  multiply- 
ing at  the  point  of  the  lesion  al  times  secrete  extremely  active  toxic- 
substances,  and  in  this  manner  give  rise,  not  to  an  infection,  bul  to 
a  more  or  less  serious  intoxication  which  is  at  limes  fatal.  This  is 
what  occurs  in  gaseous  gangrene,  diphtheria,  and  cholera.  '! 
maladies  should,  therefore,  be  considered  as  bacteriotoxemias. 

When  infection  is  generalized,  whether  a  local  lesion  is  present  or 
not,  the  microbes  penetrate  by  the  bloodvessels  or  the  lymphatic 
channels.  In  the  latter  case  they  are  first  arrested  by  the  glands, 
the  hypertrophy  of  which  testifies  sufficiently  as  to  their  incr<  - 
activity.  The  process  may  stop  here  or  may  pass  beyond  the  barrier 
opposed  by  the  glands  and  spread  in  the  blood. 

Under  natural  conditions  the  blood  is  almost  always  secondarily 
invaded.  Direct  introduction  into  the  circulation  occurs  only  in  the 
fetus,  since  the  pathogenic  agents  cannot  reach  it  otherwise  than 
by  the  sole  point  of  contact  which  it  has  with  the  external  world 
— that  is,  the  umbilical  vessels.  Infection  then  assumes  a  special 
aspect  imposed  by  its  localizations.  It  is  thus  conceivable  that  the 
liver  should  be  profoundly  altered  in  inherited  syphilis  and  that  the 
various  stages  should  not  be  separated,  as  in  the  adult.  There  is 
generalization  from  the  first:  hence,  the  absence  of  primary  lesions 
and  confusion  of  secondary  and  tertiary  stae  3. 

Whether  directly  introduced  into  the  veins  or  secondarily  invading 
the  circulatory  system,  microbes  do  not  remain  in  the  blood.  They 
rapidly  leave  this  unfavorable  medium  and  take  refuge  in  the  tissues 


108  ISFECTIOUS  DISEASES. 

and  organs.  They  do  not,  however,  distribute  themselves  equally 
in  all  the  tissues,  nor  do  they  affect  all  the  organs  in  the  same  maimer. 
The  results  vary  according  to  the  species  or  variety  under  observa- 
tion. If  a  tissue  is  already  altered,  whether  by  traumatism  or  pre- 
vious disease,  the  microbes  will  preferably  settle  in  those  parts  of 
lessened  resistance.  It  is,  therefore,  possible,  in  experimental  re- 
searches, to  cause  a  pathogenic  agent  to  colonize  at  this  or  that 
point  of  the  organism,  and  thus  create,  at  will,  nephrites,  endocar- 
dites,  osteomyelites,  and  infectious  arthrites. 

Mode  of  Action  of  Pathogenic  Microbes.  The  causes  favorable 
to  infection  having  been  described,  it  remains  to  study  in  what 
manner  microbic  development  is  followed  by  morbid  disturb- 
ances. 

Several  theories  have  been  advanced.  In  the  first,  a  mechanical 
theory,  it  is  assumed  that  the  microbes  act  simply  like  foreign  bodies; 
by  obstructing  the  capillaries  they  hinder  the  functions  of  the  organs. 
This  conception  is  hardly  deserving  of  discussion,  especially  in  view 
of  the  fact  that  the  microbes  often  remain  localized  in  some  organ 
or  tissue,  or  at  some  point  of  very  limited  extent,  as  in  the  case  of 
diphtheria,  tetanus,  and  symptomatic  anthrax. 

In  the  second  theory  it  is  assumed  that  there  is  a  struggle  for  life. 
It  is  supposed  that  the  microbes  and  the  cells  of  the  organism  vie 
with  each  other  for  the  possession  of  the  alimentary  materials  and 
oxygen  carried  by  the  blood.  When  the  question  is  one  of  a  microbe 
like  the  diphtheria  bacillus,  which  lives  upon  the  surface  of  a  mucous 
membrane,  or  of  an  anaerobic  agent,  such  as  the  bacillus  of  tetanus, 
the  oxygen  of  the  blood  is  not  needed  for  the  development  of  the 
pathogenic  agent.  As  to  the  use  of  nutritive  materials,  how  much 
of  them  can  the  microbes  consume?  We  have  no  information  con- 
cerning this  point.  However,  notwithstanding  their  active  multi- 
plication, microbes  weigh  too  little  to  give  strength  to  the  opinion 
that  their  development  starves  the  economy.  The  problem  is  more 
complex.  In  order  to  nourish  itself,  every  being  is  forced  to  secrete 
ferments  which  transform  or  modify  the  alimentary  substances. 
Miorobes  are  subject  to  this  law  and  produce  amylolytic,  inversive, 
and  proteolytic  ferments.  These  ferments  give  rise  to  substances 
which  may  serve  their  nutrition,  but  may  prove  harmful  to  the 
invaded  organism.  As  in  every  living  cell  a  double  process — assimi- 
lation and  disassimilation — goes  on  in  the  interior  of  microbes.  The 
products  of  bacterial  disassimilation,  useless  to  the  microbes,  are 


PATHOGENESIS  OF  INFECTIONS.  ]u:i 

rejected  into  the  interstitial  plasma  and  into  the  blood,  and  repre- 
sent other  noxious  substance 

Moreover,  the  substances  of  which  the  tnicrobic  protoplasm  i 
composed  are  not  harmless.  This  also  if  the  application  of  a  general 
law.  The  extracts  of  all  tissues  give  rise  to  morbid  phenomena  when 
injected  into  animals.  These  manifestations,  which  occur  even  when 
animals  of  the  same  species  are  operated  upon,  are  much  more 
marked  when  different  species  are  employed.  This  is  equally  true 
with  regard  to  bacteria.  Their  protoplasm  contain  toj  ic  ubstances 
which  may  readily  diffuse  after  their  death,  or  perhaps  even  during 
life. 

We  conclude,  therefore,  thai  infect  ious  agent  -  exerl  only  a  mechan- 
ical influence  of  secondary  importance.  They  give  rise  to  nervous 
reactions,  not  by  crowding  the  tissues,  hut  through  the  agency  of 
noxious  substances  which  they  produce  and  pas-  into  the  blood.  As 
already  stated,  infection  is  a  chapter  of  the  history  of  intoxications. 

Microbic  Poisons. 

Putrid  Poisons.     Before  the  discovery  of  pathogenic  microbes, 

at  an  epoch  when  the  nature  of  putrefactive  agents  was  not  even 
suspected,  interesting  results  had  already  been  obtained  in  the  study 
of  poisons  produced  by  fermentations. 

At  the  end  of  the  eighteenth  century  Seybert1  demonstrated  that 
the  putrefaction  of  pus,  serum,  and  infusions  of  meat  developed  in 
these  fluids  a  high  degree  of  pathogenic  power.  He  pointed  out .  for 
instance,  that  the  intravenous  injection  of  20  c.cm.  of  putrefied  serum 
into  a  dog  produced  vomiting  and  convulsions,  ending  in  death  within 
a  few  hours. 

The  question  was  taken  up  by  Gaspard,2  physician  at  St.  Etienne. 
who  pursued  a  series  of  very  remarkable  researches,  the  result-  of 
which  were  confirmed  and  completed  by  Magendie,  Virchow,  Stich, 
and,  above  all,  by  Panum,  who,  in  1856.  isolated  a  poison  the  effects 
of  which  were  comparable  to  those  of  the  toxic  substances  above 
mentioned. 

It  is  not  sufficient,  however,  to  point  out  the  toxicity  of  putrid 
substances.     The  very  element  upon  which  their  noxious  action 

1  Seybert.    Ueber  die  FauLoiss  in  Blute  an  lebenden  thierischen  Korper.    Berlin. 

2  Gaspard.     Mdmoire  physiologique  sur  les  maladies  purulentes  et  putrides.     Journal 

de  la  phys..  1S22.  1S'24. 


110  iyFECTIOUS  DISEASES. 

depends  must  be  discovered.  The  bodies  originated  during  the 
process  of  putrefaction  are  excessively  numerous  and,  moreover,  vary 
according  as  the  substances  are  exposed  to  the  open  air  or  kept  in 
closed  vessels';  according  to  the  time  putrefaction  has  lasted;  accord- 
ing to  the  nature  of  the  materials  undergoing  the  process,  etc.  The 
following  table,  nevertheless,  presents  the  principal  substances: 

\  hydrogen,    sulphuretted    hydrogen,    phosphor- 
Gas  ated    hydrogen,  protocarbonated    hydrogen, 
ammonia,  sulphohydrate  of  ammonia. 
carbonic  acid, 
phosphorated  gas,  vaguely  known  (phosphins). 

formic  (traces). 
r  volatile  gases  .     .  \  acetic. 


Acids 


butyric  (very  abundant), 
valeric. 

{acrylic, 
crotonic. 
palmitic, 
oleic, 
glycolic. 
[  polyatomic    .      .  J  lactic, 
alic. 


rgiy 

J  lac 

j  OXE 

*-  S11P 


succinic, 
findol. 
|  phenol. 

Aromatic  substances       .  J  skato1- 

J  paracresol,  orthocresol. 

r  phenylacetic,     pyroxylphe- 
[_  acids  ....  J       nylacetic. 

j  phenylpropionic,     paroxyl- 
'       phenylpropionic. 
Albuminoid  substances  -f  albuminates. 
I  peptones. 

(leucin,  leucein. 
tvrosin. 
xanthin,  hypoxanthin. 
,  complex  amido  bodies. 
Organic  bases      .       .       .  J  methylamin,  trimethylamin    etc. 
\  ethylendiamm,  amylamm,  etc. 
I  alkaloids  or  ptomains. 

Finally,  the  residues  of  putrefaction  are  rich  in  earthy  and  ammo- 
niacal  salts,  in  fats,  and  often  in  nitrates. 

So  far  as  the  gases  are  concerned,  it  is  now  known  that  they  are 
not  responsible  for  the  toxicity  of  putrid  matters.  The  same  is  true 
of  fatty  acids,  aromatic  substances,  and  amido  bodies.  There  remain 
the  albuminoids  and  the  bases.  According  to  Panum,  toxicity  must 
be  attributed  to  the  former  group.  Later  came  a  series  of  very 
notable  contributions,  due  to  Nencki,  Maas,  and,  above  all,  Brieger, 
who  thoroughly  studied  the  bases  of  putrefaction.  Selmi1  called 
them  ptomains  in  order  to  indicate  their  cadaveric  origin.  He 
recognized  that  these  ptomains  are  very  numerous;  that  some  are 
inoffensive  and  others  toxic;  that  they  resemble  vegetable  alkaloids; 

1   Selmi.     Ptomain  ad  alcaloide  cadaverici.     Bologna,  1881. 


PATHOGENESIS  OF  INFECTIONS.  Ill 

that  they  cause  pupillary  disturbances,  cardiac  irregularity   .  nar- 
cosis or  convulsions,  and  produce  death  by  arresl  oi  the  hearl  in 
systole. 
We  cannot  sum  up  all  the  works  published  on  this  interesting 

subject.  Prof,  (lautier,  who  was  first  to  point  out  the  existence  ol 
animal  alkaioids,  has  several  times  returned  to  their  study.  Bri< 
took  up  the  complete  study  and  reported  a  number  of  very  remark- 
able facts.  He  assumes  thai  al  the  beginning  of  all  putrefaction, 
lecithin  (C44H20NPO9)  is  broken  up  into  its  components,  and  the 
oxyethylic  base,  cholin  (C6H16N02),  a  substance  of  little  toxicity, 
gives  rise  to  a  vinylic  base,  nervin  (C5H18NO),  a  highly  toxic  body 
which  is  produced  simply  by  subtraction  of  one  molecule  of  water. 
The  transformation  of  lecithin  is  readily  accounted  for  by  the 
great  fragility  of  its  highly  complex  molecule.  It  is,  however,  diffi- 
cult to  say  whether  the  transformation  of  cholin  is  due  to  the 
reducing  properties  of  the  tissues  which  acquire  so  greal  an  energy 
immediately  after  death,  or  whether  it  is  already  the  work  of  micro- 
organisms. 

However  that  may  be,  here  is  a  highly  toxic  base  originated  al  the 
beginning  of  putrefaction.  Brieger  s  researches  have  established 
that  nervin  is  particularly  active  for  the  cat,  which  is  killed  by  a  few 
milligrams  of  it,  while  as  much  as  four  centigrams  are  required  to 
kill  a  rabbit.  Aside  from  nervin,  there  are  two  other  bases:  neu- 
ridin  (C5HHN,),  which  is  not  toxic,  and  methylguanidin  (Brieger  . 
which  is  tetanizing.  There  is  also  parvolin  (C9H13N),  found  by 
Gautier  and  Etard  in  the  putrid  flesh  of  the  horse:  collidin,  hydro- 
collidin,  and  two  other  bases  isolated  by  Dr.  Pouchet  and  having 
the  formulae:  one,  C7HISN20„;  the  other,  C5H12N204.  These  bodies 
are  very  toxic.  Harmless  bases,  such  as  corindin  (C^H^N),  are  also 
encountered.  On  the  whole,  the  convulsifying  alkaloids  are  dom- 
inant. 

Brieger  has  established  that  the  alkaloids  produced  in  the  human 
cadaver  vary  with  the  time  elapsed  since  the  moment  of  death.  The 
first  one  is  cholin,  which  appears  as  early  as  the  first  or  second  day 
and  disappears  toward  the  seventh  day.  On  the  third  day  neuridin 
is  produced,  which  disappears  toward  the  end  of  the  second  week. 
At  the  same  time  cadaverin  may  be  isolated,  which  increases  with 
the  progress  of  putrefaction:  then,  toward  the  fourth  day.  appear 

1  Brieger.     Untersuchungen  iiber  Ptomaine  (3  pamphlets').      Berlin.  L885-S 


112  INFECTIOUS  DISEASES. 

putrescin,  which  is  very  abundant  toward  the  fifteenth  day,  and 
saprin.  These  bases  are  not  all  toxic:  cholin  alone,  when  injected 
in  high  doses,  produces  a  few  symptoms  resembling  those  provoked 
by  muscarine 

The  truly  toxic  substances  appear  toward  the  seventh  clay.  At 
this  stage,  aside  from  trimethylamin,  which  is  of  little  toxicity,  two 
venomous  liases  are  produced,  of  which  considerable  quantities  may 
be  collected  toward  the  fifteenth  day.  One,  the  less  active,  causes 
only  alvine  evacuations;  the  other,  mydalein,  the  chemical  formula 
of  which  has  not  yet  been  determined,  is  extremely  powerful. 

When  injected  into  guinea-pigs  and  rabbits,  mydalein  causes  sali- 
vation and  lacrymation.  The  pupils  dilate,  the  ears  are  congested, 
and  the  rectal  temperature  is  raised  1.8°  to  3.6°  F.  (1°  to  2°  C). 
If  the  dose  reaches  five  milligrams  in  the  guinea-pig,  profuse  diar- 
rhea, exophthalmos,  and  then  paralysis  are  observed;  respiration 
becomes  difficult,  the  temperature  falls,  and  death  supervenes,  the 
heart  being  arrested  in  diastole. 

Ehrenberg  has  discovered  several  bases  hi  decayed  fish,  notably 
cholin,  neuriclin,  methylamin,  and  dimethylamin.  The  most  impor- 
tant body,  however,  is  ptomatropin  of  v.  Aurep,  of  which  two 
milligrams  cause,  in  a  rabbit,  mydriasis,  convulsions,  and  death  by 
arrest  of  the  heart. 

Neuridin  and  trimethylamin  are  likewise  encountered  in  putrid 
milk  and  cheese ;  also  a  base  discovered  by  Vaughan  and  designated 
tyrotoxin. 

As  has  already  been  stated,  ptomains  differ  notably  according  to 
the  time  at  which  the  products  of  putrefaction  are  studied.  Some 
appear  and  later  disappear,  to  be  succeeded  by  others.  The  chemical 
researches  which  have  revealed  these  facts,  however  interesting  they 
may  be,  ought  to  have  been  completed  by  bacteriological  studies. 
It  is,  in  fact,  a  question  whether  these  diverse  ptomains  are  produced 
during  the  various  phases  of  the  life  of  the  same  microbes,  or  whether 
their  successive  appearance  and  disappearance  depend  upon  different 
microbes  which  destroy  or  transform  the  substances  already  produced 
by  their  predecessors. 

Although  we  do  not  know  exactly  the  role  of  ferments  in  the 
genesis  of  ptomains,  we  are  better  acquainted  with  the  influence 
exerted  by  the  media.  It  is  known  that  certain  bases  are  encoun- 
tered in  all  putrefactions,  for  instance,  neuridin,  while  neurin  is  found 
only  in  the  putrefying  flesh  of  mammalia  and  muscarin  in  that  of 


PA  TH0QENE8I8  OF  INFECTIONS. 


n:; 


decayed  fish.  Likewise,  gadinin,  e1  hylenediamin,  and  I  rimel  bylamin 
are  formed  at  the  expense  of  the  flei  h  of  fish.  Finally,  dimethylamin 
has  thus  far  been  encountered  only  in  the  putrefaction  of  {."'him  or 
of  yeast. 

Kostiurinc  and  Krainsky  very  justly  remark  tlial  the  toxicity  of 
the  products  of  pni refaction  is  in  direcl  ratio  to  the  chemical  com- 
plexity of  the  substances  undergoing  putrefaction.  More  poison 
is  yielded  by  meat-  than  by  bouillon,  and  more  by  bouillon  than  by 
saline  solutions.  Toxins  are  most,  abundant  from  the  fifth  to  the 
thirtieth  day.  Furthermore,  toxins  insoluble  in  alcohol  arc  more 
active  than  those  soluble  in  this  fluid.  This  last  fact  clearly  shows 
the  importance  of  non-alkaloidal  poisons. 

There  is  no  doubt  that  whatever  cause  hinders  or  favors  the  devel- 
opment of  microbes  also  hinders  or  favors  the  development  of  putrid 
poisons.  It  will  suffice,  in  this  respect,  to  recall  the  influence  of  heat 
and  electricity.  As  to  the  role  played  by  oxygen,  opinion  is  divided. 
An  important  fact  established  by  Kijanisin  has  not,  perhaps,  been 
sufficiently  considered.  According  to  this  author,  a  greater  amount 
of  ptomains  are  produced  in  contact  with  air  than  when  the  process 
of  putrefaction  takes  place  without  air.  But  the  ptomains  are  then 
less  toxic  and  less  stable;  they,  therefore,  rapidly  disappear. 

All  the  principal  ptomains  actually  known  are  presented  in  the 
table  below,  following  Prof.  Gautier's  classification: 


f  Bocklisch, 
1  Wurtz, 

Decayed  fish, 

Xon-toxic. 

Methylamin,  CH6N, 

Normal  blood, 

" 

Dimethylamin,  C2H7N, 

Brieger, 

Putrid  yeast, 

" 

Trimethylamin,  C3H9, 

Ibid. 

Decayed  fish, 

Convulsions. 

Triethylamin,  CBH1SN, 

Ibid. 

Ibid.' 

" 

Propylamin,  C3H9N, 

Ibid. 

Putrid  gelatin, 

" 

Rutylamin,  C  HaN, 

Gautier  and 

Cod-liver  oil, 

Stupefying  and  convulsi- 

Mourgues, 

fying  poison. 

Isoamylamin,  C6A13N, 

Miiller  and 

Putrid  yeast, 

Stupefying  and  convulsi- 

Hesse, 

fying  poison. 

Amylamin,  C5H13N, 

Gautier  and 
Mourgues, 

Cod-liver  oil, 

Polyuria:  convulsions. 

Hexylamin,  C6H1SN, 

Ibid. 

Ibid. 

tt                      n 

Hesse, 

Putrid  yeast, 

"                      " 

f  Fresh  brain ; 

Xon-toxic. 

Neuridin,  C5HHN2, 

Brieger, 

■[  all  putrefac- 
l       tions, 

Ibid. 

Saprin,  C5Hl4N2, 

Ibid. 

Cadavers, 

Ibid. 

f  Brieger, 

Cadavers, 

Ibid. 

Cadaverin,  C5HUN2, 

-j  Bocklisch. 

Decayed  fish. 

Ibid. 

f  Brieger, 

Cadavers. 

Local  action,  inflamma- 
tion necrosis. 

Putrescin,  C4H,2N2, 

Bocklisch. 

Herring. 

Local  action,  inflamma- 
tion necrosis. 

Ethylenediamin.  CJT.,X";. 

Brieger. 

Putrid  codfish. 

Nasal  flux  and  mydriasis 

dyspnea  and  death. 

Methylguanidin,  C2HTX:!. 

Ibid. 

Decayed  fish, 

Excitation,  then  paral- 
ysis of  the  nervous  sys- 
tem. 

114 


INFECTIOUS  DISEASES. 


Nevrin,  C5H13XO. 

Ibid. 

Tainted  meat, 

Myosis;  salivation;  paral- 
ysis; death.  Atrophy 
(Carvello). 

Cholin,  C5lIi;,NO:, 

Ibid. 

Ibid. 

Like  muscarin,  but  action 
slight. 

Muscarin,  C5H15X03, 

Ibid. 

Putrid  codfish, 

Lacrymation,  salivation, 
convulsions. 

Mydotoxin,  C„H13X02, 

Ibid. 

Cadavers, 

Lacrymation,  salivation 
convulsions. 

Mvdin,  CgHnNOa 

Ibid. 

Ibid. 

Xon-toxic. 

Gadinin,  C7H16X62, 

Ibid. 

Decayed  fish, 

" 

Methylgadiniii,  CgH^NOo, 

Brieger, 

Tainted  meat, 

Tetanizing  poison. 

f  Xencki, 

I  CE.de  Coninck 

Pancreatic 

a              a 

Collidin,  C8H„X, 

digestion, 

Putrid  pulp, 

it              it 

Hydroeollidin,  C8Hi3N, 

Gautier  and 

Decayed  fish, 

Trembling,  convulsions, 

Etard, 

arrest  of  heart  in  dias- 
tole. 

Parvolin,  C9H13X, 

Ibid. 
f  Guareschi 

Ibid. 

Very  toxic. 

and  Mosso, 

Putrid  fibrin, 

it         a 

Coridin,  C10H15N, 

CE.  de  Con- 

{      inck 

Putrid  pulp, 

"          " 

Hydrolutidin,  C7HnN, 

j  Gautier  and 
I      Mourgues 

Cod-liver  oil, 

Trembling  paralysis. 

Scombrin,  C17H3SX4, 

(Gautier  and 
l      Etard, 
f  Gautier  and 
I      Mourgues 

Decayed  fish, 

Trembling  paralysis. 

Morrhuin,  C]9H27N3, 

Cod-liver  oil, 

Diuretic. 

Asellin,  C26H32X4, 

Ibid. 

Ibid. 

Convulsions;  death. 

Morrhuie  acid,  C9H13X03, 

Ibid. 

Ibid. 

Convulsions;  death. 

"      C7H18N0206, 

Pouchet, 

Putrid  meat, 

Convulsions;  death. 

"      C5H12X204, 

Ibid. 

Ibid. 

Convulsions;  death. 

"      CmHjoNjOo 

Guareschi 

Ibid. 

Xon-toxic. 

"      C5HuN02) 

Salkowski, 

Ibid. 

Ibid. 

Mydalein,  C5HnX02l 

Brieger, 

Human  cad- 

Fever; glandular  hyper- 

avers, 

secretions. 

Ptomatropin,  C5H'nX02, 

Aurep, 

Fish  and  meat 

Action  analogous  to  that. 

poisons, 

of  atropin. 

Ptomatocurarin,  C5HnX02, 

Harkawy, 

Putrid  yeast, 

Like  curare. 

Ptomatoconicln,  C6HnX02, 

Otto, 

Cadavers, 

Like  conicin. 

Ptomatoveratrin,  CsH^NC^, 

f  Brouardel  and  Ibid. 
1      Boutmy, 

Like  veratrin. 

Tyrotoxin,  C6HnX02, 

Vaughan, 

Spoiled  milk 
and  cheese, 

it                a 

Gastrointestinal  Putrefactions.  The  foregoing  study  of  putrid 
poisons  and  the  facts  concerning  their  production  outside  the  organ- 
ism find  numerous  applications  in  the  history  of  gastrointestinal 
putrefactions. 

The  microbes  of  the  alimentary  canal,  having  entered  with  bev- 
erages and  aliments,  must  evidently  be  the  same  as  those  which  are 
encountered  in  putrefactions  in  the  free  air.  Although  it  is  compara- 
tively easy  to  determine  the  changes  alimentary  substances  undergo 
outside  of  the  organism  through  the  agency  of  bacteria,  the  problem 
is  far  more  delicate  when  the  study  of  such  phenomena  occurring  in 
the  intestine  is  undertaken.  Here  substances  rapidly  disappear  by 
absorption,  and,  on  the  other  hand,  it  is  difficult  to  decide  which 
changes  are  clue  to  digestive  juices  secreted  by  the  organism  and 
which  alterations  are  dependent  upon  bacterial  action.    Peptones, 


PATHOGENESIS  OF  INFECTIONS.  I  I :, 

which  are  abundantly  produced  id  both  cases,  may  be  mentioned  ••>- 
anexample.  Ii  may,  therefore,  be  erroneout  to  con  ider  all  microbic 
products  harmful.  Certain  micro-organisms  are  possibly  useful  and 
must  be  considered  as  collaborators  of  the  individual  whom  they 

inhabit.  Dr.  Due.Ios  asks  whether  microbee  do  qo1  accomplish  a 
complementary  digestion  nearly  as  important  as  digestion  properly 
so  called.  Iii  fact,  it  is  certain  that  several  substance  arenol  tj 
formed  without  the  intervention  of  microbes.  Such  is  uotably  the 
case  with  cellulose.  It  can  be  seen,  therefore,  how  complex  this 
problem  is  and  how  interesting  it  would  be  to  exactly  determine  the 
role,  importance,  and  signification  of  microbic  fermentations  in  the 
processes  of  digestion  and  nutrition.1 

We  shall,  therefore,  endeavor  to  give  a  resume'  of  our  knowli 
of  this  subject. 

As  far  as  the  carbohydrates  are  concerned,  transformation  by  the 
digestive  juices  consists  in  the  production  of  dextrin  and  sugars 
(glucose, levulose, maltose).  The  microbes  form  analogous  substances 
by  saccharifying  the  starch  or  by  interverting  saccharose.  Fermen- 
tation may,  however,  go  further  and  give  rise  to  ethylic  alcohol. 
This  fact  is  of  great  interest,  since  it  perhaps  accounts  for  the 
presence  of  alcohol  in  the  liver  and  brain  of  animals  which  have 
never  ingested  this  substance  (J.  Bechamp,  Rajewski). 

There  is  another  series  of  bodies  due  to  the  action  of  figurate  fer- 
ments, namely:  lactic,  acetic,  butyric  acids,  etc.  These  acids  are 
especially  abundant  in  herbivora. 

Microbes  are  able  to  break  up  neutral  fats,  but  they  act  more 
particularly  upon  albuminoids.  Along  with  peptones,  attributed  to 
the  action  of  the  pancreatic  juice,  there  are  amidate  acids,  leucin, 
tyrosin,  hypoxanthin,  aspartic  acid,  and  cinnamic  acid :  bodies  of  the 
aromatic  series,  indol,  phenol,  skatol,  and,  finally,  various  g:  -  3, 
carbonic  acid,  hydrogen,  sulphuretted  hydrogen,  and  ammonia.  We 
have  already  stated  that  all  these  bodies  are  likewise  produced  when 
albuminoid  substances  undergo  putrefaction.  It  is  important  to 
determine  what  modifications  are  properly  due  to  the  pancreatic 
juice.  The  question  has  been  studied  by  Kiihne.  By  accomplish- 
ing artificial  digestion  in  a  medium  containing  2  per  1000  of  salicylic 
acid,  he  prevented  the  development  of  germs  and  observed  the  pro- 
duction of  peptones  and  amidate  acids,  but  he  found  no  aromatic 

1  Roger.  Art.  Physiologie  de  l'mtestin.  Diet,  encyclop.  des  se.  medicale?.  Paris, 
1889,  4  sorie,  t.  xvi. 


116  INFECTIOUS  DISEASES. 

substances  or  gases.  Other  experimenters  have  obtained  the  same 
results.  It  may,  therefore,  be  stated  that  the  intestinal  gases  and 
aromatic  substances  depend  upon  the  life  of  the  microbes.  This 
fact  explains  the  absence  of  these  substances  in  the  intestine  of  the 
fetus  and  the  newborn. 

Toxicity  of  Fecal  Matters.  Prof.  Bouchard  was  the  first  to 
show,  in  1882,  that  fecal  matters  contained  alkaloids,  some  of  which 
are  soluble  in  chloroform  and  others  in  ether.  Fecal  matter,  studied 
without  separation  of  soluble  substances,  is  highly  toxic.  According 
to  Prof.  Bouchard,  the  extract  of  seventeen  grams  is  sufficient  to 
kill  a  rabbit  of  one  kilogram  with  diarrhea  and  convulsions.  The 
poisons  are  evidently  manifold.  A  great  part  of  the  noxious  effect 
is  due  to  potassium  salts  and  ammonia.  In  fact,  if  these  salts  are 
eliminated,  the  extract  of  298  grams  of  feces  is  required  to  kill  the 
animal.  It  is  certain  that  these  figures  have  no  absolute  value  and 
that  the  toxicity  of  the  matters  is  not  constantly  the  same. 

From  a  toxicological  standpoint  it  may  be  stated  that  alcoholic 
extracts  are  generally  less  active  than  aqueous.  As  to  the  toxicity 
of  diarrheal  feces,  those  obtained  during  the  stationary  period  are 
the  most  noxious.  The  feces  of  a  patient  already  convalescent  have 
been  found  less  toxic  than  normal  fecal  matters. 

Variations  of  Gastrointestinal  Putrefactions.  The  in- 
tensity of  gastrointestinal  putrefaction  varies  considerably  with  the 
diet.  Veal,  particularly  that  of  very  young  calves,  forms  in  the  in- 
testine a  sort  of  jelly  which  is  difficult  of  absorption  and  offers  a 
favorable  pabulum  for  microbes.  On  the  other  hand,  milk  diet 
checks  putrefaction  (Biernachi)  by  reducing  the  number  of  bacteria 
(Gilbert  and  Dominici).  Even  outside  the  organism  this  fact  has 
been  observed.  If  milk  is  added  to  a  mixture  of  muscles  and  pan- 
creas, at  the  end  of  four  days  neither  indol,  skatol,  leucin,  nor  tyrosin 
is  found  (Winternitz). 

Among  the  disturbances  arising  from  autointoxications  of  intes- 
tinal origin  the  most  serious  are  those  following  ingestion  of  putrefied 
meat,  often  characterized  by  grave  and  at  times  fatal  symptoms. 
The  best  known  type  of  these  disturbances  is  botulism  or  allantiasis. 
It  has  been  well  studied  in  Germany  where  alimentary  intoxications 
are  frequent  from  the  use  of  imperfectly  cooked  sausage,  which  not 
infrequently  contains  a  great  amount  of  ptomains  and  microbes.1 

1  For  the  study  of  alimentary  intoxications,  consult :  Netter,  Des  poisons  chimiques 
qui  apparaissent  dans  les  matieres  organiques  en  decomposition,  et  des  maladies  qu'ils 


PATHOGENESIS  OF  INFECTIONS.  117 

Alimentary  poisoning  does  not,  however,  always  assume  thegp 
appearance  observed  id  typical  cases  of  botulism.  Simple  gastro 
intestinal  disturbances  often  follow  the  ingestion  of  slightly  altered 
meat  or  other  tainted  food.  There  is  vomiting,  though  not  in  every 
case,  and  especially  diarrhea,  which  is  profuse  and  extremely  fetid. 
In  these  instances  the  process  is  one  of  intoxication,  the  elements 
of  which  originate  in  the  intestine  under  the  influence  of  microbes 
contained  in  the  loud. 

Dr.  Cassedebat1  found  in  preserves  aumerous  toxic  alkaloids,  sev- 
eral of  which  resisted  boiling.  Under  the  influence  of  alkaline  bicar- 
bonates,  some  of  them  produced  a  penetrnlm<r  and  persistent  odor 
which  is  also  found  in  the  air  exhaled  by  animals  which  have  ingested 
these  toxic  bases. 

Tainted  fish  and  preserved  fish  represent  another  source  of  danger. 
Brieger,  Gautier,  and  others  have  discovered  numerous  ptomaine 
engendered  in  putrefied  fish.  Disturbances  are  frequent  as  a  result 
of  the  ingestion  of  sardines,  salmon,  and  particularly  codfish.  The 
process  is  the  same  as  in  the  case  of  meat.  We  must  take  into 
account  both  the  microbes  and  the  ptomains  which  are  secreted  by 
them,  as  was  demonstrated  by  Duvillier. 

Crustaceans  and  mollusks  decompose  more  easily  than  fish.  The 
disturbances  produced  by  tainted  prawn  and  crabs  have  long  been 
described.  One  of  the  most  remarkable  observations  is  that  reported 
by  Dr.  Rapin  (of  Lausanne)  in  1877.  Crabs  were  consumed  one  day 
without  inconvenience;  the  following  day  nine  persons  ate  some. 
After  a  period  of  incubation  of  sixteen  to  fifty-five  hours,  those 
who  had  eaten  began  to  vomit,  had  sanguinolent  diarrhea,  and 
presented  a  scarlatinoid  eruption.  One  of  the  victims  died  on  the 
twenty-third  day  with  typhoid-like  symptoms.  A  clog  which  in- 
gested some  of  the  crabs  manifested  no  disturbance. 

Such  accidents  are  most  often  due  to  preserved  lobster,  which, 
while  always  unhealthful,  is  particularly  dangerous  when  the  con- 
tainer has  been  open  for  a  day  or  two. 

A  ptomain,  tyrotoxin,  as  already  stated,  is  found  in  tainted  milk. 
The  same  is  encountered  also  in  spoiled  cheese,  ice-cream,  ices,  and 

peuvent  provoquer.  Arch.  g£n.  de  medecine.  1SS4:  Roger.  Fermentations  et  putrefac- 
tions intestinales.  Gaz.  des  hdpitaux.  March  31.  1SSS.  Polin  et  Labit.  Etude  sur  les 
empoisonnements  alimentaires.  Paris,  1S90.  (This  is  a  very  complete  and  highly 
interesting  monograph.) 

1  Cassedebat.  Bacteries  et  ptomaines  des  viandes  de  conserves.  Revue  d 'hygiene, 
1S90,  p.  659. 


J  1 8  IXFECTIO  US  DISEASES. 

certain  cakes.  Altered  milk  causes  disturbances,  especially  in  chil- 
dren, and  at  times  even  infantile  cholera. 

Condensed  milk  quite  often  becomes  altered  and  liberates  gases 
which  force,  off  the  cover  of  the  can.  Dr.  Cassedebat,  who  has  made 
a  study  of  preserved  milks,  discovered  no  microbes  in  them,  but  only 
aspergillus  and  a  few  mucedinea.  Although  harmless,  the  prepara- 
tion is  not  then  fit  for  consumption. 

Autointoxications  of  Gastrointestinal  Origin.  No  matter 
how  produced,  a  diarrhea  is  attended  by  intense  intestinal  putre- 
faction, as  we  have  already  reported.  Are  the  poisons  thus  formed 
absorbed?  Stich  believed  they  were  not.  At  the  present  day,  how- 
ever, there  can  be  no  doubt  that  they  are.  The  terrible  offensiveness 
of  the  breath  suffices  to  demonstrate  this.  In  such  cases  Prof. 
Bouchard  was  able  to  discover  considerable  quantities  of  ptomains 
in  the  feces  and  urine.  He  found  as  much  as  15  milligrams  per 
1000  grams  of  fecal  matters,  while  the  urine  contained  fifty  times 
more  than  under  normal  conditions.  In  more  serious  instances  of 
diarrhea,  fermentation  at  times  produces  ammonia  which  may  give 
rise  to  capillary  thrombosis  (fermentative  thrombosis  of  Hlava),  and, 
secondarily,  to  pseudomembranous  enterites,  with  superficial  necrosis 
of  the  mucous  membrane. 

While  putrefaction  is  increased  in  cases  of  diarrhea,  in  cases  of 
constipation,  on  the  other  hand,  stagnation  of  the  fecal  matters 
becomes  a  cause  of  intoxication  by  the  absorption  which  it  favors. 
Therefore,  a  certain  number  of  symptoms  which  are  of  the  same 
nature,  though  not  as  intense  as  those  of  diarrhea,  are  caused  by 
constipation.  In  fact,  in  both  instances  there  is  cephalalgia,  fatigue, 
nervous  disturbances,  and  tumefaction  of  the  liver.  It  is  to  be 
noted,  however,  that  in  constipation  the  matters  accumulated  in  the 
intestine,  being  excessively  hard,  do  not  readily  allow  the  transuda- 
tion of  the  toxins  they  contain. 

Constipation  exerts  curious  effects  upon  the  constitution  of  the 
blood.  By  causing  coprostasis  in  animals,  Vanni1  noticed  that  the 
red  corpuscles  diminished  in  number  and  became  less  resistant  to 
destructive  agents. 

Although  constipation  is  generally  well  borne  by  healthy  individ- 
uals, this  is  not  the  case  in  those  who  have  received  some  trauma- 
tism, in  confined  women,  and  in  persons  upon  whom  laparotomy  has 

1  Vanni.     Sull'  origin  intestinale  della  chlorosi.     II  Morgagni,  1893,  p.  533. 


PATHOGENESIS  OF  INFECTIONS.  |]!i 

been  performed.     In  more  than  one  such  <■•■>  <■  febrile  pan 
appeared  which  might  well  be  suspected  a  i  symptom*  of   epticemia, 
I > 1 1 1  which  have  vanished  with  evacuation  of  the  bowels    imp! 
the  adminisl  ration  of  an  enema.1 

The  old  surgeons  were  not,  therefore,  wrong  in  preparing  their 
patients,  and  intestinal  antisepsis  practised  for  ;i  few  dayt  before 
abdominal  operations  renders  real  service. 

Intestinal  obstruction  under  all  its  forms  internal  strangulation, 
invagination— presents  the  most  striking  picture  of  digestive  auto- 
intoxication. The  theory  of  reflex  action  cannol  accounl  for  the 
clinical  manifestations,  and  if  has  yielded  to  the  toxic  theory.  In 
fact,  Senator  has  shown  that,  by  lavage  of  the  stomach,  it.  is  possible 
to  cause  the  momentary  disappearance  of  the  symptoms  of  obstruc- 
tion and  that,  by  repeating  this  procedure,  a  cure  may  be  effected. 
This  successful  result  has  since  been  observed  by  several  physicians, 
notably  by  Drs.  Bouchard  and  Chantemesse. 

Prof.  Bouchard  has  emphasized  the  importance  of  gastric  intoxi- 
cations by  the  study  of  dilatation  of  the  stomach.  Without  intoxi- 
cation it  was  impossible  to  explain  the  various  manifestations  ob- 
served, especially  the  nervous  symptoms  which,  in  their  mildest 
forms,  are  characterized  by  prostration  and  a  feeling  of  exhaustion  at 
the  moment  of  wakening,  and,  in  their  graver  expression,  terminating 
in  aphasia,  vertigo,  tetany,  and  coma.  Fetid  sweat,  cutaneous  erup- 
tions, congestion  of  the  liver,  albuminuria,  peptonuria,  trophic  dis- 
turbances, notably  the  nodes  of  the  second  phalanges,  are  likewise 
referable  to  the  formation  of  poisons.  A  few  authorities  go  further 
and  believe  the  same  process  is  responsible  for  the  deeper  alterations 
of  the  osseous  system,  osteomalacia  in  adults,  and,  according  to 
Dr.  Comby,  rachitis  in  children. 

Poorly  digested  substances  are  easily  attacked  by  microbes  in  the 
stomach  and  intestine.  When,  however,  digestive  disturbance  is 
attended  by  hyperchlorhydria,  extremely  toxic  substances  are  pro- 
duced in  the  stomach  which  are  responsible  for  dyspeptic  tetany  and 
coma.  The  question  has  been  very  carefully  studied  by  Kulneff, 
Bouveret,  and  Devic,  but  it  is  still  unknown  what  part  is  to  be  attrib- 
uted to  microbes  in  the  genesis  of  these  poisons  and  of  ethyldiacetic 
acid.  This  acid  has  been  credited  with  an  important  role  in  the 
pathogenesis  of  comatose  phenomena,  analogous  to  those  produced 

1  Kustner.  Zur  Kritik  der  Beziehungen  zwischeu  Faecalstase  und  Fieber.  Zeitschr. 
fur  klin.  Med..  1882,  Bd.  v. 


120  INFECTIOUS  DISEASES. 

by  diabetes,  which  are  observed  in  dyspepsias,  dilatation,  ulcer,  or 
cancer  of  the  stomach,  and  after  the  ingestion  of  tainted  meat. 

The  experiments  of  Dr.  Boix1  demonstrate  that  butyric  acid  is 
capable  of  inducing  atrophic  cirrhosis;  lactic  and  valeric  acids  exert 
a  similar,  though  less  intense,  action ;  acetic  acid  is  the  most  harmful, 
for  it  is  sclerogenous  and,  at  the  same  time,  produces  cellular  degen- 
erations. 

Here  is  a  series  of  facts  which  conclusively  establish  that  secretory 
disturbances  and  putrefactions  of  the  alimentary  canal  give  rise  to 
a  great  number  of  noxious  products  which  are  capable  of  causing 
immediate  accidents  or,  in  the  long  run,  induce  visceral  lesions. 

Finally,  it  is  well  to  remark  that  in  cases  of  nephritis,  hepatic 
affections,  cardiopathies,  morphinomania,  tuberculosis,  and  evidently 
also  in  typhoid  fever  and  cholera,  there  are  profound  alterations  in 
the  stomach  and  intestine,  and,  consequently,  putrid  fermentations 
are  produced,  the  effects  of  which  are  added  to  those  of  the  primary 
disease. 

The  Toxins  of  the  Pathogenic  Microbes. 

Multiplicity  of  Microbic  Toxins.  The  idea  of  attributing  the 
development  of  infectious  diseases  to  intoxication  is  very  old.  In 
the  presence  of  bacteriology  it  seemed  for  a  moment  to  have  lost 
ground.  Soon,  however,  the  first  experimenters  themselves  began 
to  suspect  that  microbes  are  not  everything,  and  that  toxins  secreted 
by  them  played  a  role  of  prime  importance.  Diligent  and  methodic 
researches  were  undertaken  on  every  hand  and  a  great  number  of 
toxic  bases  of  microbic  origin  were  described. 

Most  of  these  bases  do  not  contain  oxygen,  and,  like  the  analogous 
alkaloids  found  in  highly  organized  plants,  they  are  not  crystallizable. 
They  are  oily,  colorless  substances,  with  a  cadaveric  odor,  seldom 
with  an  agreeable  one.  They  are  soluble  in  alcohol,  ether,  and  all 
the  usual  solvents  of  alkaloids,  and,  like  them,  form  salts  which 
crystallize.  Other  less  numerous  bases  are  oxygenated  and  conse- 
quently crystallizable. 

These  results  seemed  to  demonstrate  the  analogy  between  bacterial 
and  vegetable  alkaloids.  Soon,  however,  objections  were  raised.  It 
was  pointed  out  that  the  ptomains  extracted  from  cultures  were  far 
from  possessing  the  same  toxic  potency  as  the  total  culture,  and  did 

1  Boix.     Le  foie  des  dyspeptiques.    These  de  Paris,  1894. 


PATHOGENESIS  OF  INFECTIONS.  12 1 

not  produce  the  same  phenomena.  It  wa  recognized  that,  at  in  the 
case  of  piii  rid  poisons,  i In-  substances  soluble  in  alcohol  are  not  the 
most  active,  hut,  on  the  contrary,  tho.se  precipitated  by  this  liquid. 

It  seems  certain  that  the  bacterial  poi  on  are  very  complex  and, 
consequently,  very  unstable.  They  are,  therefore,  easily  decom- 
posed in  the  course  of  chemical  manipulations,  and  whal  i-  obtained 
at  the  end  of  the  researches  is  not  the  primary  poison,  bul  one 
derived  therefrom.  The  toxalbumins,  for  instance,  probably  contain 
an  alkaloidal  nucleus  which  is  separated  from  them  on  the  slightesl 
occasion.  Therefore,  one  can  never  be  sine  of  having  obtained  the 
primary  body.  Although  methods  of  investigation  have  been  mul- 
tiplied, no  absolutely  reliable  method  has  been  found. 

In  view  of  the  uncertainty  of  methods,  it  is  well  to  precisely  deter- 
mine the  initial  toxicity  of  the  sterilized  culture.  The  active  sub- 
stances are  subsequently  separated  without  overlooking  the  fact  that 
all  reagents,  including  alcohol,  which  is  so  frequently  employed,  may 
decompose  the  toxic  molecule.  By  combining  the  methods  the 
conviction  is  reached  that  the  majority  of  microbic  poisons  are  pre- 
cipitated by  alcohol  and  adhere  to  the  precipitates  which  form  the 
various  mineral  salts  in  the  culture  fluid.  This  is,  for  instance,  what 
occurs  with  aluminum  hydrate  and  calcium  phosphate.  In  view  of 
these  chemical  results  and  of  the  fact  that  minute  amounts  produce 
violent  results,  toxins  have  been  considered  as  ferments.  Recently, 
however,  under  the  influence  of  the  researches  of  Brieger  and  Fraen- 
kel,  they  have  been  designated  by  the  vague  term  toxalbumins,  and 
at  times  they  are  classed  with  nucleo-albumins.  It  is  to  be  remem- 
bered that  certain  microbic  poisons  possess  characters  comparable 
to  those  of  albumoses  and  peptones.  Hence,  the  names  toxal- 
bumoses  and  toxopeptones  applied  to  them. 

In  spite  of  the  divergencies  of  detail,  a  fact  is  manifest,  viz.,  that 
the  toxins  are  complex  molecules  possessing  certain  characters  of 
a  ferment.  Like  the  latter  body,  they  are  very  unstable,  adhere  to 
various  precipitates,  and  are  altered  and  decomposed  by  heat  and 
light.  Like  ferments  and  albumins,  they  are  precipitated  by  alcohol, 
and  are  only  slightly  or  slowly  dializable.  They  may.  therefore,  be 
considered  as  proteid  substances.  "They  are.'"  says  Prof.  Gautier, 
"  complicated  ptomains." 

It  has  been  asked  whether  the  question  was  rendered  any  clearer 
by  comparing  toxins  to  ferments — i.  e..  to  substances  the  nature  of 
which  is  unknown  and  which  reveal  themselves  bv  their  functions 


1 22  INFECTIO  US  DISEASES. 

.alone.  A  ferment  is  a  complex  substance  which  has  received  from 
living  substance  a  certain  degree  of  vital  activity.  It  is,  as  Buchner 
states,  "a  semiliving  matter."  At  all  events,  it  is  the  highest 
expression  of  lifeless  matter.  Under  these  conditions  the  action  of 
toxins  is  no  more  mysterious  than  that  of  ordinary  ferments.  The 
objection  which  consists  in  excluding  toxins  from  this  group  because 
they  do  not  hydrate  albumin  and  do  not  act  upon  sugar  is  of  little 
value.  This  is  like  asserting  that  pepsin  is  not  a  ferment  because 
it  does  not  convert  starch  into  sugar.  The  microbic  cell,  like  the 
animal  cell,  possesses  different  ferments;  in  other  words,  it  is  apt 
to  transmit  different  forms  of  energy  to  different  molecules. 

In  brief,  bacterial  poisons  are  complex  and  recognize  several 
origins.  The  protoplasm  of  parasites  contains  proteins  which  have 
been  well  studied  by  Buchner.  The  culture  fluid  contains  poisons 
which  are  formed  by  secretion  or  by  synthesis  and  belong  to  the  group 
of  albuminoids.  Besides  those  already  referred  to,  there  is  one  more 
toxin  to  be  mentioned,  namely,  mucin,  which  is  encountered  in  the 
cultures  of  various  microbes,  notably  that  of  the  tubercle  bacillus 
(Weyl). 

Action  of  Toxins  upon  the  Organism.  The  effects  produced 
by  microbic  toxins  vary  evidently  according  to  the  pathogenic  agent 
under  consideration.  However,  the  symptoms  observed  may  be 
divided  into  three  groups.  Some  are  produced  at  the  point  of  intro- 
duction of  the  active  substance  and  constitute  the  local  lesions. 
Others  express  the  impregnation  of  the  entire  economy,  and  are 
general  manifestations.  Lastly,  there  are  symptoms  indicating  a 
selective  action  of  the  toxin  upon  some  organ,  apparatus,  or  tissue. 

The  local  lesions  are  not  constant.  When  any  exist  they  vary, 
even  for  the  same  toxin,  according  to  the  activity  of  the  latter,  the 
point  of  introduction,  and  the  amount  of  substance  employed.  The 
researches  which  I  have  pursued  with  the  diphtheria  toxin  resulted 
as  follows:  When  injected  beneath  the  skin  it  produces,  as  is  known, 
a  very  marked  edema.  When  spread  upon  a  mucous  membrane 
exposed  to  the  air,  it  gives  rise  to  the  formation  of  false  membranes. 
If,  however,  it  is  very  active  or  the  animal  is  highly  sensitive  to  its 
action,  no  local  lesion  is  produced,  but  there  occurs  a  general  intoxi- 
cation which  rapidly  ends  in  death. 

Toxins  also  give  rise  to  general  disturbances.  These  are  the  only 
symptoms  observed  when  the  poison  is  introduced  directly  into  the 
veins.     No  matter  what  the  mode  of  introduction  may  be,  or  what 


PATHOGENESIS  OF  INFECTIONS.  123 

amount  is  introduced,  the  symptoms  are  never  manifested  instan- 
taneously. Contrary  to  what  occurs  immediately  after  an  alkaloid 
is  injected,  in  most  microbic  intoxications  there  is  a  period  of  lat< 
which  lasts  from  :i  few  hours  toadayortwo.  The  mosl  impor- 
tant genera]  manifestation  is  fever,  which  ie  accompanied  by  other 
phenomena:   urinary  disorders,  secretory  modifications,  exchanges 

of  gases,  etc. 

When  the  toxin  is  absorbed  or  when  it  is  injected  directly  into  the 
blood  it  may  produce  in  the  viscera  a  series  of  accidente  varying 
with  the  poisonand  the  animal.  They  consist  in  functional  disturb- 
ances or  in  lesions,  notably  cellular  degenerations.  It  is  conceivable 
therefore,  that  if  immediate  death  is  avoided  the  intoxicated  animal 
may  later  succumb  to  a  progressive  cachexia  which  is  sufficiently 
accounted  for  by  the  numerous  visceral  alterations  discovered  al  the 
necropsy.  In  other  instances,  an  organ  having  been  more  particu- 
larly affected,  some  organic  affection— chronic  nephritis,  myocardi- 
tis, cirrhosis,  or  myelitis— is  developed,  which  pursues  its  own  inde- 
pendent course. 

Description  of  Principal  Toxins.  Among  infectious  dise 
there  is  a  group  the  pathological  physiology  of  which  is  incompre- 
hensible if  the  action  of  a  toxin  is  not  admitted.  I  refer  to  those 
maladies  the  pathogenic  agent  of  which  remains  localized  at  the  point 
of  introduction,  viz.,  diphtheria,  tetanus,  cholera,  gaseous  gangrene, 
and  symptomatic  anthrax. 

The  diphtheria  toxin,  discovered  by  Roux  and  Yersen,  may  be  very 
active,  its  energy  not  being  necessarily  related  to  the  pathogenic 
power  of  the  culture.  A  very  virulent  bacillus  is  not  necessarily 
very  toxinogenous.  An  active  toxin  is  that  which  kills  a  guinea- 
pig  of  an  average  weight  in  a  close  of  0.1  c.cm.  With  the  bouillon  of 
Martin,  0.002  c.cm.  suffices  to  kill  a  guinea-pig  weighing  500  grams. 
If  we  remember  that  one  cubic  centimetre  of  the  fluid  gives  one  cen- 
tigram of  dry  residue,  say  0.0004  of  organic  matter,  and  that  the 
toxin  represents  only  one  part  of  this  organic  matter,  we  can  conceive 
the  prodigious  activity  of  the  diphtheritic  poison.  An  ordinary  diph- 
theria, toxin  is  sufficient  to  poison  a  weight  of  living  being  20,000,000 
times  greater  than  its  own. 

Among  the  chemical  substances  which  diminish  the  energy  of  this 
toxin  are  lactic,  acetic,  and  tartaric  acids.  However,  by  again  neu- 
tralizing the  medium,  we  may  in  great  part  at  least  renew  the 
toxicity.     Oxidizing  bodies,  such  as  potassium  permanganate,  neu- 


1 24  IXFECTIO  US  DISEASES. 

tralize  its  effects.  The  reducing  substances,  such  as  sulphuretted 
hydrogen,  are  indifferent.  Iodine  trichloride  and  iodin-water 
weaken  the  action  of  the  toxin  and  permit  its  employment  as  a 
vaccine. 

All  animals  are  not  equally  sensitive  to  the  diphtheritic  poison,  and 
those  which  are  refractory  to  the  living  bacillus  are  so  to  the  toxin. 
The  guinea-pig  is  readily  poisoned  by  it ;  the  rabbit  is  less  susceptible, 
and  the  dog  still  less.     The  mouse  and  the  rat  endure  high  doses. 

Subcutaneous  injection  produces  a  local  edema,  which  is  often 
very  marked,  and  congestion  of  the  corresponding  ganglia.  In  the 
rabbit  it  is  followed  by  the  formation  of  pseudomembranes,  often 
very  extensive  and  thick,  occupying  the  larynx,  trachea,  and  at 
times  the  intrapulmonary  bronchial  tubes.  Upon  the  exposed  mu- 
cous membranes  the  lesion  remains  local.  When  introduced  into  the 
alimentary  canal,  this  toxin  produces  no  effects. 

Subcutaneous  or  intravenous  injection  of  the  toxin  is  not  followed 
by  any  immediate  symptoms.  At  the  end  of  a  period  which  varies 
with  the  activity  of  the  poison  and  the  quantity  introduced,  the 
guinea-pigs  become  cold  and  are  seen  to  stay  in  a  corner  of  their 
cage ;  they  subsequently  fall  into  a  somnolent  state  and  die  in  hypo- 
thermia. Rabbits  frequently  suffer  from  diarrhea.  At  the  necropsy 
pulmonary  congestion  and  edema,  pleural  effusion,  congestion,  and 
at  times  hemorrhages  into  the  suprarenal  capsules  are  found  in  the 
guinea-pig.  In  the  rabbit  the  dominant  changes  are  intense  conges- 
tion of  the  liver  and  kidneys,  with  fatty  degeneration  of  the  cellsr 
while  the  suprarenal  capsules  are  generally  intact. 

When  very  small  doses  are  injected,  paralytic  phenomena,  espe- 
cially in  the  rabbit,  may  be  observed  during  life.  At  the  necropsy 
alterations  of  the  nervous  system  are  frequently  discovered.  It  is  also 
in  such  cases  that  myocarditis  is  found,  which  has  been  well  studied 
by  Mollard,  Regaud,  and  others. 

The  Tetanic  Toxin.  In  the  early  studies  of  tetanus  experimenters 
resorted,  as  is  commonly  the  case,  to  complex  methods,  which  subse- 
quently were  replaced  by  simpler  procedures.  Brieger,  who  was  the 
first  to  investigate  the  poison  of  tetanus,  endeavored  to  obtain  chemi- 
cally defined  bodies.  By  experimenting  upon  the  arm  of  a  man 
suffering  from  tetanus,  and  upon  impure  cultures,  he  obtained,  apart 
from  the  putrefactive  bases  already  known,  four  new  bases :  tetaninr 
whose  chemical  composition  is  established  by  him  to  be  C13H30N2O4r 
and  causes  trismus  and  then  generalized  tetanus  in  the  mouse; 


PATHOGENESIS  OF  INFECTIONS.  126 

tefanofoxin,  which  produces  convulsions  or  paral}  es;    pa  mot< 
which  gives  rise  to  clonic  and  ionic  spasm  ;  lastly,  a  base  which 
stimulates  the  salivary  and  lacrymal  secretion  . 

Kitasato  and  Weyl,  experimenting  with  pure  cultures,  detected 

tetanin  and  traces  of  totanotoxin,  hut  these  bases  aci  only  in  enor 
mous  doses.     As  a  matter  of  fact,  the  true  poison  is  of  a  different 
nature,  as  has  been  demonstrated  perfectly  by   Kund   Faber.     Thifi 
author  simply  filters  the  culture  fluid  through  porcelain  and  obtains 

a  toxin  resembling  diastases,  which  is  destroyed  by  :ileohol  or  a  tem- 
perature of  149°  F.  (65°  C).     Injected  into  animals,  it   produces 

tetanus  after  a  period  of  incubation.  It  behaves,  therefore,  like 
the  diphtheritic  toxin. 

At  present  it  is  known  that  the  tetanic  poison  is  more  of  an  albu- 
minoid nature  than  a  ptomain.  Obtained  by  filtration  of  cultures, 
the  poison  is  of  such  strength  that  yiruinro  c-cm-  suffices  to  kill  a 
mouse.  Dr.  Nicolas,  having  accidentally  pricked  his  own  skin 
with  the  point  of  a  needle  charged  with  the  toxin,  was  taken  sick, 
after  four  days,  with  tetanus  which  proved  to  be  of  a  benign  char- 
acter. 

Two  theories  have  been  advanced  with  regard  to  the  pathological 
physiology  of  tetanus:  one,  originated  by  Autokeatow  and  developed 
by  Courmont  and  Doyon,  admits  an  action  of  the  poison  upon  the 
sensory  nerves;  the  other,  defended  by  Bruner,  assumes  increased 
excitability  of  the  nerve  centres — i.  e.,  a  modification  analogous  to 
that  produced  by  strychnine. 

The  Cholera  Toxin.  The  choleraic  poison  was  first  studied  by  Petri, 
who  considered  it  as  a  toxopeptone,  and  by  Hueppe  and  Scholl,  who 
cultivated  the  vibrio  in  egg  albumin  without  being  able  to  completely 
remove  from  their  preparations  of  toxin  sulphuretted  hydrogen  and 
alcohol  (Gruber  and  Wiener). 

The  question  has  further  been  studied  by  "Westbroock,  who  ob- 
tained a  hypothermizing  poison:  by  Sanarelli,  who  isolated  a  toxin 
acting  through  the  alimentary  canal:  by  Brieger  and  Fraenkel.  who 
prepared  an  unstable  protein.  The  most  important  contributions 
have  come  from  Pfeiffer  and  Ransom.  The  results  are,  however, 
contradictory.  Pfeiffer  asserts  that  the  poison  resides  in  the  body 
of  the  microbe,  while  Ransom  contends  that  the  toxin  is  a  soluble 
substance  which  resists  a  temperature  of  212°  F.  (100°  C.)  and.  in 
small  doses,  causes  death  in  collapse:  in  high  doses,  its  action  is 
instantaneous. 


1 26  ISFECTIO  US  DISEASES. 

The  question  was  taken  up  and  completely  studied  by  Drs.  Metch- 
nikoff,  Roux,  and  Taurelli-Salimbeni.  These  authorities  began  by 
exalting  the  vibrio  by  means  of  a  very  ingenious  procedure,  which 
consists  in  cultivating  it  in  small  capsules  of  collodion  introduced 
into  the  peritoneum  of  guinea-pigs.  When  the  microbe  has  become 
quite  energetic,  it  is  transferred  to  a  fluid  containing  2  per  cent,  of 
gelatin,  2  per  cent,  of  peptone,  and  1  per  cent,  of  sea  salt.  The  most 
active  poison  is  obtained  on  the  third  or  fourth  day.  A  dose  of 
0.3  c.cm.  per  100  grams  kills  a  guinea-pig  in  sixteen  to  twenty-four 
hours.  This  poison  differs  from  the  cholera  and  diphtheria  toxins 
in  that  it  resists  boiling.  It  is  destroyed  by  sunlight,  precipitates 
ammonium  sulphate  and  strong  alcohol.  Injected  into  guinea-pigs, 
it  produces  prostration,  meteorism,  and  diarrhea.  The  animals 
succumb  in  hypothermia. 

Toxins  of  Gaseous  Gangrene  and  Symptomatic  Anthrax.  The  bacilli 
of  gaseous  gangrene  and  of  symptomatic  anthrax  are  two  very  closely 
related  anaerobics.  They  resemble  the  preceding  microbes  in  their 
tendency  to  remain  localized,  although  they  invade  the  organism 
more  easily,  at  least  when  the  question  is  one  of  small  laboratory 
animals. 

The  poison  of  gaseous  gangrene,  studied  by  Roux  and  Chamber- 
land,  and  more  completely  by  Besson,  when  injected  in  a  dose  of 
3  c.cm.  to  5  c.cm.  into  the  peritoneal  cavity  of  guinea-pigs  weighing 
from  450  to  600  grains  produces  grave  symptoms  with  hypothermia. 
The  animals  recover,  however.  Introduced  subcutaneously,  the 
poison  gives  rise  to  considerable  edema  and  at  times  to  an  eschar. 
The  latter  result  is  of  great  interest,  since  it  elucidates  the  mechan- 
ism of  gangrenous  lesions.  To  kill  a  guinea-pig  of  300  to  400 
grams,  the  injection  of  5  c.cm.  to  10  c.cm.  is  required. 

It  is  not  easy  to  state  whether  the  poison  of  gaseous  gangrene  is 
identical  with  or  analogous  to  that  of  symptomatic  anthrax,  since 
researches  have  not  been  pursued  under  altogether  similar  condi- 
tions. 

The  Toxin  of  Anthrax.  We  now  come  to  that  group  of  microbes 
which  manifest  a  tendency  to  invade  the  entire  organism.  The  list 
may  properly  be  headed  by  the  bacillus  anlhracis  and  the  microbe 
of  chicken  cholera. 

The  preparation  of  the  anthrax  toxin  seems  to  be  quite  difficult, 
and  its  study  has  been  the  subject  of  numerous  contradictory  re- 
searches.   The  poison  seems  to  remain  long  enclosed  in  the  bacterial 


PATHOGENESIS  OF  INFECTIONS.  \2l 

cellule.     It  diffuses  tardily  and  only  in  media  prepared  in  a    pedal 
manner. 

The  best  work  on  this  subject  is  due  to  Marmier.  This  author 
cultivated  the  bacillus  in  a  medium  containing  40  per  cent,  of  peptone 
and  4  per  cent,  of  glycerin.  The  active  substance  i  extracted  by 
means  of  ammonium  sulphate  and  alcohol,  [f  the  culture  has  been 
kept  at  96.8°  F.  (36°  C),  the  toxin  is  Blight  in  amounl ;  it  i-  abundant 
if  the  medium  has  been  kept  at  68°  F.  (20°  C.)  for  a  fortnight.  This 
toxin,  injected  into  animals,  causes  a  U'vcv  which  is  ushered  in  toward 
the  fourth  hour,  and  reaches  its  maximum  the  following  day.  Diar- 
rhea makes  its  appearance,  the  animals  become  thin,  cachectic,  and, 
after  convulsions,  succumb  in  hypothermia. 

Toxins  of  the  Bacilli  of  Hemorrhagic  Septicemias.  Some  researches 
have  been  made  on  various  agents  of  hemorrhagic  septicemia-,  not- 
ably those  of  hog  cholera.  DeSchweinitz  found  albuminoids (suchole- 
albumins)  and  a  ptomain  (sucholetoxin)  toxic  for  the  guinea-pig. 
Novy  isolated  a  toxalbumin  and  a  protein.  Voges1  has  also  done 
important  work  bearing  on  this  subject.  His  conclusion  is,  with 
regard  to  the  toxins,  that  the  poison  is  contained  in  the  microbic 
cells.  This  is  proved  by  treating  the  cultures  with  chloroform,  car- 
bolic acid,  or  tricresol.  Subjection  to  a  temperature  of  122°  F. 
(50°  C.)  or  140°  F.  (60°  C.)  or  to  ebullition  for  ten  minutes  likewise 
yields  good  results.  Absolute  alcohol  exerts  a  very  marked  destruc- 
tive action  upon  the  toxin. 

Among  the  septicemic  agents  observed  in  man,  proton*  vulgaris 
may  be  mentioned.  Its  sterilized  cultures  are  almost  as  active  as 
the  living  cultures  and  produce  about  the  same  general  as  well  as 
local  effects.  According  to  Foa  and  Bonome,  the  chief  toxin  is  nervin . 
which  is  abundantly  present  in  the  cultures. 

Toxins  of  the  Bacillus  Septicus  Putidus.  The  soluble  products  of  the 
B.  septicus  putidus  are  very  active.  Half  a  cubic  centimetre  is  suffi- 
cient to  kill  one  kilogram  of  rabbit  within  five  to  fourteen  days.  A 
dose  of  20  c.cm.  to  30  c.cm.  kills  in  a  few  hours,  and  45  c.cm.  proves 
fatal  in  a  few  minutes.  In  such  acute  cases  there  is  paresis  and 
convulsions,  death  supervening  by  arrest  of  respiration. 

The  Pyocyaneus  Toxin.  Like  the  preceding,  this  bacillus  may  be 
observed  in  man,  but  its  chief  interest  is  due  to  the  experimental 

1  O.  Voges.  Kritisehe  Studium  und  exp.  Untersuchungen  iiber  die  Bakterien  der 
h:\moiTkagiscken  Septikamie  und  die  durch  sie  bewirkter  Krankkeitsformen.  Zeitsekr. 
fur  Hygiene  und  Infektionsfrrankheiten,  1S96,  Bd.  xxiii. 


128  IXFECTIOUS  DISEASES. 

researches  to  which  it  has  been  subjected.  Everyone  is  aware  of 
the  interesting  work  of  Charrin,  who  was  able,  with  sterilized  cultures, 
to  produce  in  animals  symptoms  identical  to  those  caused  by  the 
microbe  itself. 

The  Toxins  of  Colon  Bacillus.  On  account  of  the  important  role 
which  the  colon  bacillus  plays  in  the  organism,  even  under  normal 
conditions,  it  is  proper  to  give  it  special  attention  in  this  cursory 
review. 

The  soluble  products  secreted  by  this  microbe,  or  rather  by  the 
various  bacteria  constituting  the  group  of  colon  bacilli,  have  been 
well  studied  by  Denys  and  Brion,  and  particularly  by  Gilbert.1  From 
these  researches  it  is  shown  that  the  toxins  of  the  colon  bacillus  are 
of  varying  potency  according  to  the  virulence  of  the  germ;  moreover, 
they  are  the  more  powerful  the  older  the  culture.  Nevertheless,  to 
cause  death,  Gilbert  had  to  inject  very  large  doses,  varying  from 
37  c.cm.  to  74  c.cm.  per  kilogram  of  animal. 

Rabbits  which  receive  the  sterilized  culture  become  weak  and  the 
muscles  manifest  fibrillary  trembling.  Convulsions  and  nystagmus 
then  supervene.  The  third  stage  is  characterized  by  a  violent 
tetanus,  to  which  the  animal  succumbs.  The  nervous  phenomena 
depend  upon  spinal  changes  easily  discoverable  in  frogs.2  The  intoxi- 
cation in  this  animal  is  comprised  in  three  stages:  a  stage  of  initial 
paresis,  a  stage  of  muscular  hyperexcitability,  and  a  stage  of  par- 
alysis. The  tracings  which  I  have  obtained  clearly  show  that  the 
poison  acts  upon  the  spinal  cord  and,  secondarily,  upon  the  muscles. 

The  poison  of  the  colon  bacillus,  the  effects  of  which  have  just  been 
referred  to,  is  constantly  produced  in  the  intestine.  A  part  of  it  is 
arrested  and  transformed  by  the  intestinal  epithelium,  as  was  demon- 
strated by  Denj^s;  another  part  penetrates  the  organism.  However, 
since  absorption  is  effected  by  the  portal  vein,  the  liver  may  exercise 
a  protective  role,  and,  as  a  matter  of  fact,  we  have  established  that 
this  gland  is  capable  of  arresting  and  transforming  the  intestinal 
poisons.  That  portion  escaping  the  action  of  the  liver  is  eliminated 
by  the  urine  and  contributes  to  the  toxicity  which  this  secretion 
presents  under  normal  conditions.  Gilbert  justly  remarks  that  cer- 
tain symptoms  are  common  to  intoxications  produced  either  by  the 

1  Gilbert.  Des  poisons  produits  par  le  bacille  intestinal  d'Escherich.  Soc.  de  biol- 
ogie,  February  25,  1893,  p.  214. 

2  Roger.  Etude  sur  la  toxicite  des  produits  solubles  du  B.  coli  communis.  Arch, 
de  physiol.,  July  1,  1893. 


PATHOGENESIS  OF  INFECTIONS.  129 

urine  or  by  the  colon  bacillus,  and  that,  moreover,  when  putrefac- 
tions of  the  intestine  are  checked  by  antiseptics,  the  toxicity  of  the 

urine  is  at  the  same  time  reduced. 
Under  various  pathological  conditions  the  virulence  of  the  colon 

bacillus  increases.  In  some  instances,  the  microbe  invades  the  organ- 
ism and  produces  therein  the  soluble  substances  the  effect*  of  which 
have  just  been  referred  to.  These  effects  are  more  pronounced  w  hen 
the  protective  organs  of  the  economy  are  more  or  less  altered  by 
the  disease. 

The  author  made  an  experimental  study  of  the  toxin-  produced 
by  a  colon  bacillus  representing  the  cause  of  a  variety  of  dysentery.1 

The  cultures  of  this  colon  bacillus  inoculated  into  rabbits  proved 
extremely  virulent.  A  few  drops  injected  into  a  vein  caused  death 
in  less  than  a  day,  at  times  in  six  hours.  This  microbe  produced 
very  strong  toxins  in  the  culture  media.  When  the  culture  medium 
was  composed  of  equal  parts  of  bouillon  and  serum,  instead  of  simple 
bouillon,  the  results  were  more  interesting.  At  the  end  of  eight  days 
the  culture  was  sterilized  by  means  of  chloroform,  which  was  subse- 
quently removed  by  decantation  and  evaporation.  The  fluid  thus 
prepared  was  so  very  toxic  that  ten  drops  injected  into  the  veins  of 
a  rabbit  of  2  kilograms  sufficed  to  produce  fever,  diarrhea,  and, 
finally,  death  in  twenty-four  or  forty-eight  hours.  With  a  second 
sample,  furnished  by  a  bacillus  exalted  by  passages  through  animals, 
18  c.cm  to  20  c.cm.  caused  death  within  an  hour  or  two. 

One  of  the  first  symptoms  produced  by  the  toxin  is  diarrhea, 
which  is  at  times  extremely  profuse,  amounting  to  a  continuous 
evacuation.  Hence  the  rapid  loss  of  weight  suffered  by  the  animals. 
The  toxin  prepared  with  the  exalted  microbe  exerted  a  far  more 
energetic  action,  but  gave  rise  to  very  little,  if  any.  diarrhea.  It 
may,  therefore,  be  admitted  that  the  intestinal  flux  eliminates  not 
only  the  poisons  originated  in  the  digestive  canal,  but  also  the  noxious 
substances  which  may  have  penetrated  the  economy. 

The  Toxins  of  the  Pyogenic  Microbes.  The  pus  cocci  constitute  a 
group,  at  the  head  of  which  we  would  place  the  staphylococcus.  The 
staphylococcic  toxin  is  of  considerable  interest  with  reference  to  the 
study  of  suppuration.  It  will  be  treated  in  the  chapter  devoted  to 
this  question.     The  poison  may  likewise  give  rise  to  general  mani- 

1  Roger.  Les  toxines  du  colibacille  de  la  dysenterie.  Ann.  de  la  soc.  de  med.  de 
Gand,  1900.  p.  139.    Le  colibacille  de  la  dysenterie.    Presse  med.,  July  4.  1900. 

9 


130  INFECTIOUS  DISEASES. 

testations.  In  this  respect,  however,  its  history  is  not  so  important 
as  that  of  the  streptococcus. 

The  study  of  the  soluble  products  of  the  streptococcus  was  first 
made  by  Manfredi  and  Traversa.  In  a  highly  remarkable  memoire 
these  authors  have  shown  that  the  cultures  of  this  microbe,  freed 
from  all  figurate  elements  by  means  of  porcelain  filters,  are  toxic  for 
the  frog,  guinea-pig,  and  rabbit.  In  the  last-named  animal,  thirty 
to  fifty  minutes  after  subcutaneous  injection  of  the  filtered  fluid,  a 
certain  degree  of  somnolence  is  observed,  then  a  slight  paresis  of  the 
extremities.     In  most  cases  the  animal  recovers  in  a  few  days. 

To  obtain  the  toxic  substances,  the  author1  cultivated  the  strep- 
tococcus in  thick  bouillon  protected  from  the  air  by  a  layer  of  oil. 
The  fluid  was  filtered  at  the  end  of  fifteen  clays  and  injected  into  the 
veins  of  a  certain  number  of  rabbits.  The  fatal  dose,  which  varied 
somewhat  from  one  culture  to  another,  oscillated  generally  between 
13  c.cm.  and  20  c.cm.  per  kilogram.  After  the  injection  the  animals 
remained  in  a  state  of  somnolence;  the  next  day  they  presented  a 
very  profuse  diarrhea.  Death  supervened  at  the  end  of  two  or  three 
days. 

To  establish  the  nature  of  the  toxin  the  filtered  fluid  was  treated 
with  ten  times  its  volume  of  absolute  alcohol.  The  resulting  abun- 
dant precipitate  was  washed  with  alcohol  and  reclissolved  in  a  7  per 
1000  salt  solution.  The  alcoholic  fluids  were  united  and  evaporated 
at  a  low  temperature.  The  residue  was  then  treated  with  salt  water. 
Two  extracts  were  thus  obtained  which  were  studied  separately. 
The  alcoholic  extract  did  not  prove  to  be  toxic.  On  the  other  hand, 
the  aqueous  extract  gave  rise  to  the  same  disturbances  as  the  total 
culture,  except  that  higher  doses  were  required. 

The  toxin  of  the  streptococcus  when  submitted  to  a  temperature 
of  219.2°  F.  (104°  C.)  is  considerably  weakened.  This  is  true  of  the 
total  culture  as  well  as  of  the  aqueous  extract. 

The  Toxin  of  the  Pneumococcus.  The  toxin  of  the  pneumococcus, 
which  has  been  prepared  and  well  studied  by  Drs.  Carnot  and  Four- 
nier,  is  so  active  that  a  few  drops  of  it  injected  into  the  lung  produce 
a  focus  of  pneumonia  characterized  by  flatness,  crepitant  rales,  and 
bronchial  breathing.  At  the  necropsy,  fibrinous  pneumonia,  com- 
parable to  that  observed  in  man,  is  discovered.     By  varying  the 

1  Roger.  Action  des  produits  solubles  du  streptocoque  de  PeYysipele.  Soc.  de 
biologie,  July  4,  1891.  Contribution  a  P£tude  experimentale  du  streptocoque  de  Pery- 
sipele.     Revue  de  m<§d.,  December,  1892. 


PA  THOQ ENE8I8  OF  XNFEi  TIO N8.  1 :;  ] 

experimental  conditions,  oilier  varieties  of  pulmonary  lesii 

he  produced,  sucli  ns  liemorrhagic  pneumonia,  gray  hepatization, 

and  abscess  of  the  Lung. 

The  Toxin  of  Typhoid  Fever.      The  I  yplioid    lo.\in    has  been  Studied 

by  Brieger and  Fraenkel,  who  believed  il  bo  bea  toxalbumin,  Sana- 
relli  experimented  with  extracts  obtained  by  macerating  the  bacilli 
for  six  months.    The  toxin  thus  prepared  produces  hypothermia, 

abdominal  meteorism,  mucous  and  sanguinolentstools.  Death  occurs 
in  coma. 

According  to  Chantemesse  and  Ramond,  the  toxin  is  rapidly 
destroyed  in  the  cultures  by  oxidation.  These  authors  employ  ae  a 
medium  a  bouillon  prepared  with  spleen  digested  by  fresh  pepsin 
derived  from  the  stomach  of  a  pig.  The  poison  manifests  the  great- 
est energy  on  the  fifth  or  sixth  day.  It  is  very  active  for  the  guinea- 
pig,  rabbit,  sheep,  dog,  and  especially  the  horse.  If  the  amount 
injected  into  a  rabbit  is  very  small,  hyperthermia  is  the  result :  if  it 
is  large,  then  hypothermia  occurs.  At  the  same  time  diarrhea  makes 
its  appearance,  followed  by  respiratory  and  circulatory  disturbances. 
The  necropsy  reveals  congestion  of  the  intestine  and  abdominal 
organs,  liver,  kidneys,  and  spleen.  In  his  more  recent  researches, 
Chantemesse  made  a  very  minute  analysis  of  the  action  exerted  by 
this  toxin  upon  the  heart  and  nervous  system. 

Toxins  of  Glanders.  We  shall  mention  one  more  toxin,  that  of 
glanders,  which,  according  to  Finger,  produces  rapid  death,  or,  if  the 
dose  is  less  strong,  a  progressive  cachexia  accompanied  by  paralytic 
manifestations.  Babes  and  Motoc  isolated  from  the  cultures  a  sub- 
stance insoluble  in  alcohol  and  possessing  a  very  marked  thermogenic 
action.  Its  injection  produces  spasms,  and,  if  the  injections  are 
repeated,  nephritis  results,  and  death  supervenes  in  marasmus. 

Poisons  Found  in  Infected  Organisms.  Aside  from  the  poisons 
due  to  the  microbe,  the  diseased  organism  itself  elaborates  some. 
These  may  be  divided  into  three  groups: 

1.  Poisons  produced  b}^  the  organism  under  the  influence  of  patho- 
genic microbes.  This  group  includes  poisons  which  cannot  originate 
in  culture  media,  the  microbes  attacking  the  constituent  elements  of 
the  invaded  organism  directly  or  through  the  ferments  which  they 
secrete. 

2.  Poisons  derived  from  the  alimentary  canal  in  the  course  of 
infections,  in  which  putrefaction  is  always  increased. 

3.  Poisons  derived  from  disassimilation,  which  is  increased  and 


132  INFECTIOUS  DISEASES. 

perverted.  To  this  cause  are  probably  clue  the  profound  modifica- 
tions occurring  in  the  chemical  constitution  of  the  organism  in  the 
course  of  febrile  maladies.  The  alkalinity  of  the  blood  is  diminished : 
instead  of  representing  4  to  5  grains  (238  to  280  milligrams)  of  soda, 
it  corresponds  to  no  more  than  about  three-fourths  of  a  grain  (40 
milligrams),  the  change  being  due  to  the  increase  of  acids,  notably 
formic,  acetic,  diacetic,  ^-oxybutyric,  and  lactic  acids,  and  volatile 
fatty  acids. 

The  increased  acidity  results  in  increased  elimination  of  ammonia. 
The  extractive  material  and  amidate  bodies  increase  at  the  same 
time.  The  nutritive  disturbances  engendered  by  infections  are  also 
expressed  by  other  modifications  in  the  excretion  of  nitrog- 
enous bodies — i.  e.,serinuria,  globulinuria,  albumosuria,  and  probably 
acetonuria.  To  these  should  be  added  toxalbumins,  which  were 
detected  by  Alt  in  the  vomitus  of  choleraic  patients,  and  by  Brieger 
and  Wassermann  in  the  urine  of  an  erysipelatous  subject. 

Toxicity  of  the  Blood  and  Urine  in  Some  Infections.  The 
toxicity  of  the  blood  may  be  increased  in  very  notable  degree.  Very 
grave  accidents  and  death  are  the  results  when  10  c.cm.  to  15  c.cm. 
of  the  serum  of  a  rabbit  suffering  from  anthrax  is  injected  into  a 
healthy  rabbit.  Bose  demonstrated  that  the  serum  of  cholera- 
stricken  patients  injected  into  rabbits,  in  the  proportion  of  3  c.cm. 
to  5  c.cm.  per  kilogram,  causes  death  within  twelve  to  sixteen  hours 
with  choleriform  symptoms. 

The  toxic  substances  have  most  often  been  sought  for  in  the  urine. 
Some  have  been  content  to  study  its  total  toxicity;  others  have 
endeavored  to  isolate  from  the  urine  some  definite  substance ;  in  most 
cases  a  ptomain.  In  1882  Prof.  Bouchard  detected  in  the  urine  of 
typhoid  patients  the  presence  of  alkaloids,  of  which  he  obtained  as 
much  as  one  milligram  a  day.  Two  years  later  Drs.  Lepine  and 
Guerin  made  the  same  observation  in  cases  of  typhoid  fever  and  of 
pneumonia.  Dr.  Lepine  further  recognized,  with  Dr.  Aubert,  that 
the  toxic  substances  of  organic  nature  are  considerably  increased  in 
febrile  urine,  while  mineral  poisons  suffer  no  variation. 

The  second  method  consists  in  studying  the  toxicity  of  the  urine 
without  reference  to  the  nature  of  the  poison  to  which  it  is  due. 
It  is  by  this  procedure  that  Prof.  Bouchard  revealed  the  special 
properties  possessed  by  the  urine  of  cholera  patients.  It  may  be 
stated,  without  exaggeration,  that  his  work  is  the  fundamental  study 
on  this  subject,  and  has  been  taken  as  a  model  for  further  researches. 


PATHOGENESIS  OF  INFECTIONS.  183 

Dr.  Lupine  discovered  a  toxic  alkaloid  in  the  urine  of  pneumonia 
patients.  Tin-  amount  of  the  alkaloid  increasei  in  proportion  to  the 
intensity  of  the  disease  and  possesses  the  power  to  arresl  the  heart 
in  diastole.  The  presence  of  alkaloids  in  the  mine  of  pneumonia 
cases  has  been  confirmed  by  the  researches  of  Griffiths  and  Albu. 

Researches  pursued  with  Dr.  Gaume1  showed  us,  contrary  to  all 
expectation,  that  the  toxicity  of  the  urine  diminishes  as  the  di 
progresses.  At  the  end  of  the  stationary  stage  the  toxicity  i-  often 
no  more  than  half  or  one-third  of  the  normal.  Later,  at  the  moment 
of  defervescence,  a  urotoxic  crisis  occurs,  and  the  toxicity  again 
rises  above  the  normal.  In  souk;  instances  it  exceeds  but  slightly 
the  normal  toxicity;  in  others  it  acquires  a  double,  treble,  or  even 
quadruple  value.  This  excessive  toxicity  lasts  twenty-four  to  forty- 
eight  hours.  During  convalescence  the  urine  presents  a  variable 
toxicity,  which  may  be  equal  to,  below,  or  above  the  normal. 

Similar  researches  have  been  made  by  various  experimenters  upon 
the  toxicity  of  the  urine  in  erysipelas,  variola,  scarlatina,  typhoid 
fever,  tetanus,  malaria,  influenza,  tuberculosis,  and  leprosy.  It  is 
curious  to  note  that,  in  most  cases,  the  poison  detected  in  patients 
is  of  alkaloidal  nature,  while  the  microbic  poisons,  as  discovered  in 
artificial  cultures,  belong  to  the  category  of  albuminoids  and  pep- 
tones. This  lack  of  harmony  is,  perhaps,  clue  to  the  fact  that  the 
poisons  are  multifarious  and  that  substances  other  than  bases  have 
not  sufficiently  been  looked  for.  It  is  possible,  however,  that  microbes 
act  in  the  bodies  of  animals  otherwise  than  in  culture  media.  Finally, 
it  may  be  supposed  that  the  ptomains  are  produced  by  the  organism 
itself  reacting  in  a  special  maimer  under  the  new  conditions  imposed 
upon  it.  As  a  matter  of  fact,  apparently  insignificant  changes  suffice 
to  completely  modify  the  physiological  action  of  organic  compounds. 

Griffiths  has  rightly  remarked  that  a  toxic  base.propylglycocyamin. 
is  found  in  the  urine  of  patients  suffering  from  various  affections. 
This  base  is  no  other  than  creatin,  an  inoffensive  substance,  in  which 
an  atom  of  hydrogen  has  been  replaced  by  the  radical  propyl.  This 
simple  change  has  resulted  in  a  complete  transformation  in  the  phys- 
iological action.  Klebs  has  reported  a  similar  example.  According 
to  him,  cholera  nostras  is  dependent  upon  methylguanidin,  a  violent 
poison  derived  from  guanidin,  a  harmless  body,  by  substitution  of  a 
group  of  methyl  for  an  atom  of  hydrogen. 

1  Roger  et  Gaume.    Toxicite  de  l'eurine  dans  la  pueurnonie.     Revue  de  rued..  188! 


1 34  IXFECTIO  US  DISEA  SES. 

It  is  conceivable  that,  in  the  same  disease,  according  to  a  variety 
of  secondary  circumstances,  autointoxication  may  be  due  to  various 
substances.  The  results  of  researches  have,  therefore,  not  always 
agreed.  The  toxicity  of  the  urine  varies  from  one  patient  to  another. 
In  two  individuals  suffering  from  the  same  disease  the  urine  of  one 
may  contain  alkaloids,  while  that  of  the  other  may  be  free  from 
them. 

Aside  from  the  poisons  secreted  by  the  microbes  or  produced  under 
their  influence,  there  are  also  those  arising  from  lack  of  oxidation  in 
the  course  of  various  affections.  This  point  has  been  well  estab- 
lished by  the  researches  of  Dr.  Albert  Robin.  As  a  result  of  the 
insufficient  transformation  of  toxic  substances  in  the  more  or  less 
disturbed  organs,  poisons  reach  the  kidneys  in  excessive  quantities. 
If  these  emunctories  are  in  a  normal  condition,  the  urine  eliminates 
the  noxious  bodies ;  if  not,  they  are  accumulated  in  the  economy  to 
be  thrown  out  at  the  time  of  crisis. 

Rich  and  encouraging  as  are  the  results  of  researches  touching  the 
question  of  intoxications  in  infectious  diseases,  other  facts  of  great 
interest  are  sure  to  be  brought  to  light  to  clear  up  contradictions 
and  obscurities. 


(Ml  A  I'TKR    V. 

MICROBIC  ASSOCIATIONS. 

Experimental    Demonstration  of  the    Rdle  of  Microbic   A    ocial  ociation  of 

Saprophytes  wiili  Anaerobic  and  Aerobic  Microbei  ,     M<  chaniam  of  Microbic  \ 
(•ijit.ions."    Imposition  mid  Criticism  of  Varioti     Cheorii         Application  of  Exp 
mental  Data  to  Clinical   Medicine.     Simultaneous  Evolution  of  Two  Infed 
Successive  Infections.     Secondary   [nfections.     Cqmbined   [nfections  in  the  Skin, 
in  the    Nasobuccopharyngeal    Cavity,  in  the    Respiratory  Apparatus,  and    the 
Alimentary  Canal.     Secondary  Septicemias,  Their  Importance  inthe  Course  and 
in  Consequence  of  Acute  [nfections.     Secondary  [nfections  in  Chronic  D 
Favorable  [nfluence  of  Certain  Secondary  [nfections. 

Experimental  Demonstration  of  the  Role  of  Microbic  Asso- 
ciations. The  analysis  of  clinical  facts  had  Long  demonstrated  the 
frequency  of  microbic  associations.1  It  had  boon  established  that, 
in  a  groat  number  of  cases,  two  or  several  bacteria  simultaneously 
or  successively  invaded  the  organism.  To  better  comprehend  the 
signification  of  these  clinical  revelations  it  was  necessary  to  transfer 
the  question  upon  experimental  ground  and  discover  the  effects  pro- 
duced by  simultaneous  inoculation  of  two  different  microbes,  one 
pathogenic,  the  other  inoffensive.  This  the  author  undertook  to  dr. 
in  1889. 

The  author  first  studied  the  results  of  association  of  the  B.  pro- 
digiosus  with  an  anaerobic  microbe,  namely,  with  a  specimen  of 
septic  vibrio  which  was  not  pathogenic  for  the  rabbit.2  He  next 
experimented  with  the  bacillus  of  symptomatic  anthrax.3 

Considered  as  a  simple  saprophyte,  the  B.  prodigiosus  may  be 
injected  into  the  muscles  of  a  rabbit  without  producing  any  notable 
disturbance.  One  or  2  ccni.  of  a  gelatin  culture  are  well  endured. 
While,  however,  this  bacillus  does  not  cause  death,  it  does  not  seem 
to  be  altogether  harmless. 

1  Hericourt.     Les  associations  microbiennes.     Revue  de  med..  1887,  p.  095. 

2  Roger.  Quelques  effets  des  associations  microbiennes.  Soc.  de  biologie.  January 
19,  1SS9. 

3  Roger.    Inoculation  du  charbon  symptomatique  au  lapin.    First  note,  ibid..  February 
2 ,  1889.     Second  note,  ibid.,  March  30,  1SS9.     Des  produits  niicrobiens  qui  favorisent  1. 
developpenient  des  infections.     Compte  Rendu  de  l'Acad.  des  Sc.  July  29,  1889.     Con- 
tribution a  l'etude  experimental  du  charbon  symptom.     Rev.  de  med..  March  10  and 
June  10,  1S91. 


136  IXFECTIO  US  DISEASES. 

The  second  microbe  which  the  author  used,  the  bacillus  of  symp- 
tomatic anthrax,  is  an  anaerobic  bacillus  possessing  most  of  the 
characters  of  the  septic  vibrio,  but  no  pathogenic  power  whatever  for 
the  rabbit.  It  rapidly  kills  the  guinea-pig,  producing  in  this  animal 
the  well-known  lesions  of  gaseous  gangrene.  If  the  serous  fluid  of 
a  guinea-pig  thus  infected  is  inoculated  into  a  rabbit,  no  disturbance 
results.  I  have  injected  with  impunity  quantities  varying  from  two 
to  ten  drops.     Of  fifteen  rabbits  thus  treated,  none  succumbed. 

Here,  therefore,  are  two  microbes  which,  even  in  considerable 
doses,  give  rise  to  no  disturbance  when  inoculated  into  the  rabbit. 

When,  however,  one  or  two  drops  of  the  gangrenous  serous  exudate 
of  the  guinea-pig  is  mixed  with  0.75  c.cm.  or  1  c.cm.  of  a  culture  of 
the  B.  prodigiosus,  and  the  mixture  injected  into  the  muscles  of  the 
thigh  of  a  rabbit,  this  animal  dies  in  less  than  twenty-four  hours;  at 
times  in  eight  hours. 

The  necropsy  reveals  lesions  absolutely  characteristic  and  alto- 
gether similar  to  those  observed  in  the  guinea-pig. 

The  microbe  which  had  proved  fatal,  owing  to  the  association  of 
the  B.  prodigiosus,  had  acquired  a  slight  increase  of  virulence.  The 
serous  exudate  reinoculated  into  a  second  rabbit  caused  the  death 
of  the  latter,  but  the  edema  fluid  of  this  second  animal  inoculated 
into  a  third  produced  no  effect. 

In  a  second  series  of  researches  the  author  employed  as  auxiliary 
agents  other  microbes  than  the  B.  prodigiosus.  It  is  readily  under- 
stood that  the  field  of  these  experiments  was  limited,  for  the  author 
could  not  employ  those  bacteria  the  inoculation  of  which  was  fatal 
to  the  animal.  Hence,  the  pyogenic  agents  were  chosen  for  the 
purposes  of  the  research,  and  first  the  staphylococcus  aureus,  the 
most  widely  distributed  of  all.  The  specimen  employed  was  derived 
from  a  furuncle,  and  was  not  very  virulent.  It  was  found  necessary 
to  inject  0.6  c.cm.  of  a  completely  liquefied  gelatin  culture  with 
0.02  c.cm.  of  symptomatic  anthrax  in  order  to  overcome  the  resist- 
ance of  the  rabbit.  When  the  same  amount  of  staphylococcus  was 
injected  alone  a  large  abscess  was  the  result,  which  healed  after 
spontaneous  rupture. 

The  bacillus  proteus  vulgaris  proved  more  active.  The  injection 
of  0.25  c.cm.  of  a  liquefied  gelatin  culture  sufficed  for  the  develop- 
ment of  symptomatic  anthrax. 

Finally,  the  pyogenic  streptococcus  was  experimented  with.  In 
this  case,  however,  the  addition  of  1  c.cm.  of  a  bouillon  culture  to 


MIOBOBIO  ASSOCIATIONS.  137 

0.02  com.  of  symptomatic  anthrax  culture  wa    followed  by  do 
symptoms. 

It  is  hardly  necessary  to  say  thai  no  absolute  value  Bhould  be 
placed  upon  these  results.  The  action  of  the  auxiliary  microbe  musl 
vary  with  the  specimen  employed.  However,  the  experiments  above 
reported  suffice  to  establish  the  synergic  rdle  of  two  microbes.  In 
other  words,  it  demonstrates  thai  two  bacteria  which  are  harmlese 
for  the  animal  when  taken  separately,  become  pathogenic  and  rapidly 
produce  dc:dh  when  they  co-operate. 

Microbic  Products  Favorable  to  Infection.  Lei  us  now  en- 
deavor to  enter  a  little  deeper  in  this  resc-ireli  ,'iinl  poinl  out  the 
mechanism  set  at  work  by  the  auxiliary  microbes  in  order  to  bring 
about  the  development  of  a  virulent  disease  in  an  animal  naturally 
immune. 

To  explain  the  action  of  auxiliary  microbes  two  hypotheses  may 
be  advanced:  (1)  The  microbes  may  be  supposed  to  act  as  living 
elements  by  some  mechanical  action,  or  by  appropriating  nutritive 
substances  and  oxygen  destined  for  the  tissues,  thus  weakening  the 
resistance  of  the  latter.  (2)  It  may  be  assumed  that  the  microbes 
secrete  chemical  substances  which  locally  alter  the  muscles  or,  being 
absorbed,  disturb  the  general  state  of  the  invaded  organism. 

The  idea  that  the  auxiliary  microbes  act  by  soluble  products  is  in 
harmony  with  the  results  obtained  in  various  infections.  The  author, 
therefore,  first  attempted  to  verify  the  accuracy  of  this  hypothesis. 
For  this  purpose  it  was  evidently  sufficient  to  inject  into  the  muscles 
a  mixture  of  symptomatic  anthrax  and  a  certain  amount  of  a  culture 
deprived  of  living  microbes.  To  secure  the  latter  the  author  steril- 
ized the  fluids  by  heat.  By  employing  a  culture  of  B.  prodigi<>>u* 
which  was  kept  for  ten  minutes  in  the  autoclave  at  a  temperature 
of  219.2°  F.  (104°  C),  he  noticed  that  the  fluid  thus  prepared  acted 
like  the  living  culture.  It  was  only  necessary  to  employ  a  little 
more  of  the  sterilized  culture,  namely,  1  c.cm.  to  1.5  com.  This 
partial  weakening  of  the  fluid  was  to  be  expected.  Aside  from 
the  alterations  which  heat  may  produce  in  the  active  substance, 
account  is  to  be  taken  of  the  products  secreted  by  the  living  microbe 
when  developing  the  muscular  tissue. 

Similar  results  were  obtained  with  sterilized  cultures  of  proteus 
and  of  staphylococcus.  It  was  found  necessary  to  employ,  on  an 
average,  0.5  c.cm.  of  the  former  and  1  c.cm.  of  the  latter. 

The  immunity  of  the  rabbit  from  symptomatic  anthrax  may  be 


138  IXFECTIO  US  DISEASES. 

strengthened  by  injecting  into  its  veins  a  few  drops  of  anthrax  serous 
exudate.  As  soon  as  this  is  done  the  animal  becomes  refractory 
against  the  microbic  association.  Rabbits  which  had  received  two 
injections  at  an  interval  of  eight  days  were  inoculated  a  week  after 
with  the  two  microbes.  They  resisted  perfectly.  A  few  of  them 
presented  only  a  local  lesion.  The  thigh  became  edematous;  then, 
a  few  days  later,  the  swelling  subsided.  In  a  certain  number  of  cases 
an  abscess  was  formed  which  soon  healed  spontaneously. 

The  author  then  made  an  attempt  to  vaccinate  the  animals  against 
the  effects  of  the  microbic  association  bjr  previously  inoculating  them 
with  the  other  microbe — i.  e.,  the  B.  prodigiosus.  Living  or  sterilized 
cultures  were  repeatedly  injected  beneath  the  skin  or  into  the  veins. 
The  results  were  always  negative  in  so  far  as  the  animals  died  when 
they  were  subsequently  inoculated  with  the  two  microbes. 

These  various  results  prove  to  what  extent  the  experimenter  is 
able  to  vary  morbid  aptitudes.  The  rabbit  is  by  nature  immune 
from  symptomatic  anthrax.  If,  along  with  the  virus,  the  soluble 
substances  secreted  by  another  microbe  be  introduced,  the  disease 
is  surely  contracted.  If,  however,  an  intravenous  injection  of 
anthrax  virus  is  previously  made  so  as  to  reinforce  the  natural 
immunity,  the  animal  is  protected  against  the  effects  of  the  microbic 
association. 

The  rabbit  is  not  the  only  animal  whose  immunity  may  be  over- 
come by  means  of  microbic  associations.  The  results,  as  experi- 
ments have  shown  the  author,  are  similar  when  the  pigeon  is  operated 
upon,  which  is  also,  as  is  known,  refractory  to  symptomatic  anthrax. 

Examples  of  Microbic  Associations.  The  bacillus  of  sympto- 
matic anthrax  is  an  anaerobic  agent  to  which  that  of  tetanus  may 
naturally  be  compared.  Therefore,  the  study  of  microbic  associa- 
tions might  well  be  resumed  with  this  microbe.  That  is  what  Drs. 
Vaillard,  Vincent,  and  Rouget  have  done.1 

Experimenters  first  recognized  that  cultures  of  the  tetanus  bacillus 
injected  into  an  animal  not  very  sensitive  to  this  infection — viz.,  the 
rabbit — produces  a  fatal  disease  if  a  small  amount  of  B.  prodigiosus 
is  at  the  same  time  introduced.  Extending  experimental  analysis 
further,  investigators  established  that  the  spores  of  tetanus  are 
incapable  of  germinating  in  a  living  organism  or  of  giving  rise  to  the 

1  Vaillard  et  Vincent.  Contribution  a  l'etude  du  tetanos.  Ann.  de  PInst.  Pasteur, 
January,  1891.  Vaillard  et  Rouget,  Contribution  a  l'etude  du  t6tanos.  Ibid.,  June,  1892 . 
Note  au  sujet  de  l'etiologie  du  tetanos.     Ibid.,  November,  1893. 


MKJIIOIUC  ASSOCIATIONS.  139 

slightest  disturbance.  The  culture  produce  symptom  because 
the  soluble  products  contained  in  it,  and  not  by  virtue  of  the  figurate 
elements.  The  soluble  substances  act  rapidly  and  induce  a  fatal 
intoxication.  If  care;  is  taken  to  wash  ;ill  Loxic  product  from  the 
spores,  their  injection  produces  no  effect.  II,  however,  ;i  small 
amount  of  a  living  culture  of  />'.  prodigiosus  is  injected  ;ii  the  same 
lime,  tetanus  develops.  Under  natural  conditions  the  phenomena 
.•ire  analogous:  the  leianus  s|>ores  enter  contused  i  is  mes  or  penet  rate 
along  with  common  bacteria,  which  promote  their  development.  All 
microbes,  however,  are  not  capable  of  playing  I  he  pari  of  an  auxiliary. 
The  bacillus  of  Friedlaender,  (he  slaphylocoeeus  aureus,  i  1m-  trep- 
tococcus,  and  />'.  suhli/is  ha,ve  remained  withoul  effeet. 

Since  the  first  publication  of  the  researches  on  microbic  associa- 
tions the  question  has  been  pursued  by  ;i  very  greal  number  of 
experimenters,  among  whom  may  especially  be  mentioned  Blach- 
stein,  Zumpf,  and  Metchnikoff,  on  microbic  associations  in  cholera; 
Sanarelli  on  the  role  of  the  colon  bacillus  in  the  development  of 
typhoid  infection;  Mosny  on  the  influence  of  the  soluble  producl 
staphylococcus  in  the  production  of  pneumonia,  and  Feltz,  who 
demonstrated  that  the  toxins  of  the  colon  bacillus  increase  the  viru- 
lence of  the  bacillus  anthracis  and  of  the  staphylococcus  aureus. 

Favorable  Influence  of  Certain  Microbic  Associations.  Although 
in  the  majority  of  cases  microbic  associations  considerably  aggravate 
the  prognosis  of  infections,  the  reverse  may  also  be  observed.  One 
microbe  may  hinder  the  evolution  of  another,  and  the  organism  finds 
an  unexpected  ally  in  one  of  the  two  pathogenic  agents. 

The  starting  point  of  researches  upon  this  subject  was  the  work 
of  Emmerich,  who  declared  that  guinea-pigs  which  had  resisted  an 
inoculation  of  streptococcus  became  refractory  to  anthrax.  Six 
hours  after  subcutaneous  injection  into  a  guinea-pig  thus  prepared 
the  anthrax  bacteria  were  altered.  At  the  end  of  twelve  or  seven- 
teen hours  they  were  destroyed. 

Taking  up  this  research,  Pawlowsky  noticed  that  previous  or 
simultaneous  inoculations  of  either  pneumobacillus,  streptococcus, 
or,  particularly,  staphylococcus,  arrested  the  development  of  anthrax. 
While,  however,  these  microbes  confer  immunity  against  subcuta- 
neous inoculations  of  anthrax,  they  are  far  less  powerful  against 
intravenous  inoculations.  By  injecting  two  microbes,  one  after  the 
other,  into  the  veins,  death  may  be  delayed,  but  the  animals  are  not 
saved.     These  interesting  facts  have   been   confirmed  by  further 


1 40  IXFECTIO  US  DISEASES. 

researches.  In  the  experiments  of  Pavone  guinea-pigs  which  had 
previously  been  injected  with  typhoid  bacilli  resisted  anthrax  infec- 
tion. 

To  explain  the  mode  of  action  of  microbes  which  prevent  infection 
the  theory  of  antagonism  of  bacteria  has  been  proposed. 

Pasteur  had  long  recognized  the  importance  of  studying  the  devel- 
opment of  two  or  more  microbes  in  the  same  medium.  In  1SS7  he 
pointed  out  that  the  bacillus  anthracis  hardly  develops  in  a  bouillon 
which  has  been  used  for  the  culture  of  the  bacillus  of  chicken  cholera. 

These  observations,  however,  were  not  conclusive.  Garre  was  one 
of  the  first  to  undertake  systematic  researches  upon  this  interesting 
question.  He  discovered  that  culture  media  which  are  exhausted 
by  the  vegetation  of  a  microbe  are  unfit  for  the  development  of 
other  bacteria.  The  exactness  of  this  result  has  been  recognized  by 
various  experimenters.  On  the  other  hand,  it  has  long  been  known 
that  when  various  microbes  are  cultivated  in  the  same  medium,  a  sort 
of  struggle  for  existence  takes  place  among  them.  Some  die ;  others 
survive.  If  successive  cultures  are  made,  the  same  competition 
occurs,  and  finally,  only  one  species  remains  in  the  culture.  This 
is  an  instance  of  true  natural  selection.  The  most  resistant  species 
is,  as  a  rule,  the  one  most  widely  distributed  and  the  least  pathogenic. 
Such,  however,  is  not  always  the  case.  One  bacterium  may  favor 
the  development  of  another.  An  aerobic  microbe,  by  appropriating 
the  oxygen,  may  aid  the  multiplication  of  an  anaerobic  bacterium. 
When,  however,  associated  vegetation  is  possible,  modifications  in 
the  chromogenic,  toxicogenic,  and  pathogenic  functions  may  occur. 
The  toxin  of  tetanus,  for  instance,  increases  the  virulence  of  certain 
pathogenic  microbes  (Roncali,  Klein).  The  streptococcus  causes 
the  diphtheria  bacillus  to  secrete  a  greater  amount  of  toxin  (von 
Schreider) . 

Mechanism  of  Microbic  Associations ;  Exposition  and  Criticism 
of  Different  Theories.  Do  the  various  results  above  described 
enlighten  us  as  to  the  key  of  microbic  associations?  Can  it  be 
assumed,  for  instance,  that  a  microbe  hinders  or  favors  an  infection 
because  it  produces  substances  which  are  harmful  or  favorable  to  the 
pathogenic  agent?  This  doctrine  has  been  advocated  by  some,  but 
it  seems  to  me  unacceptable.  It  is  contradicted  by  the  results 
obtained  by  studying  the  association  of  sterilized  cultures  of  B. 
jsrodigiosus  with  bacillus  anthracis  or  with  the  bacillus  of  sympto- 
matic anthrax.     By  injecting  beneath  the  skin  of  the  ear  of  a  rabbit 


MIOBOBIO  ASSOCIATIONS.  ]  11 

a  mixture  of  0.01  c.cm.  of  a  cull  ure  of  bacillu,  anihraeU  and  0.5  c.cm. 
of  a  culture  of  the  B.  prodigiosus  sterilized  ai  230°  F.  (110°  C 
local  lesion  characterized  by  swelling,  redness,  and  heal ,  occur  ,   The 
control  animals  inoculated  with  pure  anthrax  presenl  a  little  edema 
without  redness  or  heat,  and  succumb  from  the  second  to  the  fifth  i 
The  others  survive  the  inoculation  and  die  later  than  the  controls.1 

The  resisting  animals  have  doI  become  immime.    They  die  when 
they  are  subsequently  reinoculated  beneath  the  skin  of  the  ear.    A 
special  phenomenon  only  is  produced,  namely,  an  enormous  ed 
invading  Hie  eyes,  the  cheeks,  the  forehead,  and  gh  ing  a  very  strange 
aspect  to  the  face. 

If  the  same  experiments  are  repeated  upon  guinea-pigs,  diamet- 
rically contrary  results  are  obtained.  The  animals  which  receive  the 
mixture  of  anthrax  and  B.  prodigiosus  present  early  and  very  exten- 
sive edemas  and  succumb  several  days  before  the  controls.  The 
differences  are  quite  clear  when  cultures  of  low  virulence,  permitting 
a  sufficiently  long  survival  are  employed.  The  effects  are  identical 
whether  the  B.  prodigiosus  be  injected  into  the  same  point  where 
the  anthrax  is  or  into  a  different  region. 

Reciprocally,  Deuschmann  has  shown  that  the  B.  prodigiosus, 
which  facilitates  the  development  of  symptomatic  anthrax  in  the 
rabbit,  exerts  a  contrary  action  upon  the  guinea-pig.  While  it 
abolishes  the  immunity  of  the  refractory  animal,  it  enables  the 
animal  which  is  naturally  susceptible  to  resist  a  virulent  inoculation. 

These  facts  again  demonstrate  how  hazardous  it  is  to  jump  to 
generalizations.  They  are  also  of  special  interest  because  they  serve 
to  disprove  all  the  theories  offered  in  explanation  of  the  mechanism 
of  microbic  associations. 

These  theories  are  already  very  numerous.  They  call  to  their  aid 
either  modifications  of  diapedesis  or  of  phagocytosis,  or  an  action 
of  microbic  toxins  upon  the  pathogenic  agent.  According  to  Drs. 
Vaillard  and  Vincent,  who  have  studied  the  adjuvant  action  of  living 
cultures  of  the  B.  prodigiosus  upon  tetanus,  the  phagocytes  are  busy 
incorporating  the  saprophyte  bacilli,  and,  while  they  are  engaged  in 
this  easy  pursuit,  the  tetanus  bacillus  has  time  to  develop  and  to 
secrete  its  toxins.  This  view  was  no  longer  tenable  after  Drs.  Vail- 
lard and  Rouget  recognized  that  the  soluble  products  acted  like  the 
virulent  cultures.     They  then  were  led  to  modify  then*  theory  and 

1  Roger.  Influence  des  produits  solubles  du  R.  prodigiosus  sur  1 'infection  charbon- 
neuse.     Soc.  de  biologie.  May  10,  1S05. 


142  INFECTIOUS  DISEASES. 

argue  that  the  microbic  products  exert  a  chemiotactic  action.  These 
products  possess  the  double  property  of  attracting  the  leucocytes  and 
of  necrosing  them. 

According  to  Prof.  Bouchard,  the  toxins  act  by  influencing  the 
vasomotor  centres.  According  as  they  favor  or  hinder  reflex  vaso- 
dilatation, they  favor  or  hinder  diapedesis  and  phagocytosis  and, 
consequently,  assist  the  organism  or,  on  the  contrary,  the  microbe. 
Among  others,  the  following  objection  is  to  be  made  against  this 
theory:  In  order  to  paralyze  the  vasomotor  centres,  considerable 
quantities  of  toxin  must  be  introduced ;  in  order  to  produce  infection 
the  injection  of  a  fraction  of  a  drop  suffices.  What  is,  however,  still 
more  grave  is  the  fact  that  this  theory,  as  well  as  that  of  Vaillard, 
does  not  explain  the  variability  of  results  obtained  according  to  the 
species  operated  upon  and  the  microbe  employed.  If  the  B.  pro- 
digiosus  prevents  phagocytosis  when  it  is  associated  with  tetanus  or 
with  symptomatic  anthrax,  why  does  it  favor  phagocytosis  when  it 
is  combined  with  the  bacillus  anthracisf 

If,  on  the  contrary,  it  be  admitted  that  microbic  toxins  act  by 
modifying  the  germicidal  power  of  the  blood,  it  is  plain  that  the 
supervening  changes  may  inhibit  one  species  of  bacteria  and  favor 
the  action  of  another.  I  recognize  that  my  explication  is  no  more 
than  a  hypothesis  needing  experimental  control.  However,  it  is 
supported  by  some  facts.  According  to  Nissen,  the  germicidal  power 
of  the  blood  is  abolished  when  a  sufficiently  large  amount  of  microbes 
is  injected  into  the  veins.  Bastin,  after  confirming  Nissen's  discovery, 
obtained  analogous  results  by  employing  cultures  sterilized  by  means 
of  heat,  chloroform,  or  ether.  He  further  established  that  there  is 
a  relationship  between  the  dose  injected  and  the  degree  of  diminution 
of  the  germicidal  power.  Lastly,  he  has  pointed  out  that  when  the 
germicidal  power  is  abolished  for  one  species,  say  for  the  staphylo- 
coccus aureus,  it  may  be  so  with  regard  to  another,  the  B.  lactis 
aerogenes,  for  instance.  If  it  is  some  day  recognized  that  the  ger- 
micidal power  is  increased  for  certain  agents,  the  demonstration  will 
be  perfect.  For  the  time  being,  however,  the  explanation  presented 
by  us  is  only  an  hypothesis,  but  it  is  the  only  one  in  accord  with  the 
results  thus  far  obtained  by  experimentation. 

Clinical  Study — Combined  Infections. 

Clinical  observation  first  led  to  experimental  researches  on  microbic 
associations.     In  its  turn,  experimentation  sheds  light  upon  facts 


MICROBIC  ASSOCIATIONS.  I  I.; 

observed  in  the  sick  and  enables  us  to  comprehend  bhemechani  m  of 

combined  infections. 
There  are  four  orders  of  facts  to  be  considered: 

1.  Two  exogenous  infections  evolving  simultaneously  in  the  Bame 
subject. 

2.  Two  infections  evolving  successively. 

3.  An  acute  infection  attacks  an  individual  who  has  previously 
suffered  from  a  chronic  infection. 

4.  An  intercurrenl  infection  favors  the  developmenl  of  pathogenic 
germs  which,  until  then,  vegetated  withoul  any  inconvenience  upon 
the  skin  and  mucous  membranes.  This  last  group  is,  perhaps,  the 
most  important  of  all. 

Simultaneous  Occurrence  of  Two  Infections.  When  two  infec- 
tions develop  simultaneously,  they  evolve  side  by  side,  each  preserv- 
ing its  special  characters.  An  aggravation  in  their  evolution  may 
sometimes  be  observed.  Even  then,  however,  the  two  proa 
remain  distinct.  Such  is  the  case,  for  instance,  when  two  eruptive 
fevers  develop  in  the  same  individual.  In  most  cases,  measles  and 
scarlatina  coexist.  The  two  eruptions  may  appear  at  the  same  time, 
each  developing  at  points  of  the  skin  which  have  been  spared  by  the 
other.  Each  disease  behaves  as  if  it  were  alone,  except  that,  in  many 
cases,  the  eruptions  last  for  a  shorter  time  than  usual.  The  prog- 
nosis is  in  nowise  modified. 

We  cannot  dwell  upon  all  possible  combinations.  Variola,  scar- 
latina, vaccinia,  typhoid  fever,  and  whooping-cough  may  occur  one 
with  another.  Measles  may  coexist  with  whooping-cough,  typhoid 
fever  with  pneumonia,  and,  in  hot  countries,  with  malaria,  and, 
though  very  seldom,  even  with  tuberculosis. 

In  its  various  stages,  syphilis  may  be  associated  with  other  infec- 
tions. At  the  start  it  may  be  a  "mixed  chancre."'  resulting  from 
the  simultaneous  inoculation  of  the  syphilitic  virus  and  that  of  soft 
chancre.  In  these  cases,  the  soft  chancre,  the  period  of  inoculation 
of  which  is  shorter,  appears  first.  A  few  days  after  its  base  becomes 
hard,  then  the  soft  chancre  is  healed  while  the  syphilitic  lesion  per- 
sists. The  chancre  is,  therefore,  mixed  but  for  the  middle  period 
of  its  existence.  A  similar  evolution  occurs  in  vaccinosyphilitic 
chancre.  The  vaccinal  eruption  appears  and  runs  its  regular  course. 
Afterward,  toward  the  twenty-fifth  day,  the  chancre  makes  its 
appearance  beneath  the  crusts  of  even  the  cicatrices  of  the  pustules. 
At  a  more  advanced  stage,  syphilis  may  coexist  with  tuberculosis. 


144  IXFECTIO  US  DISEA  SES. 

The  result  is  hybrid  clinical  types  and  events  difficult  of  interpre- 
tation. 

Secondary  Infections.  The  author  has  several  times  seen  patients 
convalescent  from  one  eruptive  fever  contract  another.  The  second 
infection  generally  runs  its  regular  course.  More  interesting  are 
those  cases  in  which  diphtheria  makes  its  appearance  in  the  course 
of  another  disease,  especially  of  scarlatina  or  measles.  It  is  then  a 
question  whether  this  secondary  diphtheria  is  really  due  to  an  addi- 
tional infection  from  without  or  whether,  on  the  contrary,  it  is 
dependent  upon  exaltation  of  the  Loeffler  bacillus  already  present 
in  the  throat  as  an  innocent  resident.  Without  absolutely  rejecting 
the  latter  interpretation,  I  believe  the  former  is  true  in  the  majority 
of  cases,  if  not  in  all.  Out  of  a  total  of  4030  patients  affected  with 
scarlet  fever  or  measles  that  have  been  treated  in  my  wards,  only 
one  case  of  secondary  diphtheria  was  observed.  This  was  in  a  woman 
who  had  been  in  a  ward  close  to  one  where  diphtheria  cases  were 
treated.  It  is  well  to  recall  that  diphtheritic  manifestations  which, 
until  a  few  years  ago,  were  of  frequent  occurrence  in  hospitals  for 
children,  have  become  altogether  rare  since  prophylactic  measures 
and  isolation  of  different  classes  of  patients  has  been  rigorously 
practised.  It  is,  therefore,  not  unfair  to  conclude  that  secondary 
diphtheria  originates  by  contagion. 

Development  of  tuberculous  manifestations  subsequent  to  an  acute 
infection  is  not  rare.  In  most  cases  the  course  is  rapid.  At  times 
the  process  is  one  of  caseous  pneumonia.  More  often,  however, 
tubercles  invade  the  whole  organism. 

Typhoid  fever  is  not  rare  in  consumptives.  It  runs  its  course  in 
a  regular  manner.  Subsequently,  however,  tuberculosis  assumes  an 
acute  course. 

The  influence  of  erysipelas  is  more  complex.  Its  influence  on 
pulmonary  tuberculosis  is  never  favorable,  and  is  at  times  harmful. 
As  to  its  action  upon  local  tuberculosis,  principally  upon  lupus,  opin- 
ion is  divided  because,  perhaps,  the  results  are  variable.  Erysipelas 
developing  in  an  old  lesion  favors  its  cicatrization.  It  may  likewise 
cause  improvement  in  neoplasms,  epitheliomata,  and,  above  all, 
sarcomata.     It  acts  in  the  same  way  in  lymphadenia. 

It  may,  therefore,  be  concluded  that  while,  in  the  majority  of 
instances,  an  intercurrent  acute  infection  aggravates  a  pre-existing 
chronic  infection,  it  may,  in  some  cases,  favor  the  healing  of  some 
atonic  lesions. 


MICBOBIO  ASSOCIATIONS.  1  j:, 

Combined  Infections  of  the  Skin.     In  the  majority  of  disei 
affecting  the  skin  or  the  mucous  membrane    communicating  with 
the  exterior,  mixed  infection  is  unavoidable,  and  il  i    often  difficult 
to  determine  the  part  due  to  the  main  agenl  and  thai  ascribable  to 
auxiliary  agents. 

The  role  of  secondary  infections  is  of  considerable  importance  in 
cases  of  variola.  The  pustules  contain  a  greal  number  of  pyogenic 
microbes  From  cutaneous  sources.  When  the  patienl  dies  thestaphy- 
lococcus,  and  particularly  the  streptococcus,  and  al  times  the  pneu- 
mococcus,  are  found  in  Hie  organs.  The  question  is  to  ascertain  the 
respective  r61e  of  the  specific  agenl  and  of  the  secondary  microbes. 
Is  it  not  to  the  latter  thai  the  fatal  termination  is  due?  And  can 
it  not  be  assumed  that  the  gravity  of  confluent  variola  depends 
mostly  upon  the  extent  of  suppuration,  absorption  of  secreted  prod- 
ucts in  the  pustules,  and  general  infection  of  the  organism  by  pu- 
cocci?  It  is  evidently  impossible  to  precisely  answer  this  question. 
All  that  can  be  said  is  that  the  microbe  of  smallpox  is  a  genuine  pus 
coccus,  but  one  of  special  nature,  since  it  produces  pus  particularly 
rich  in  mononuclear  leucocytes.  This  fact  authorizes  us  to  limit  the 
role  of  superadded  agents.  Clinical  observation  already  pointed  to 
this  conclusion,  for  according  as  the  subject  is  or  is  not  partially 
immune — according,  for  instance,  as  his  organism  has  or  has  not  been 
modified  by  previous  vaccination — suppuration  runs  its  course  or  is 
cut  short.  Notwithstanding  the  presence  of  pus  cocci  in  the  pustules. 
the  eruption  is  aborted. 

Combined  Infections  in  the  Throat.  What  has  just  been  said 
concerning  the  skin  may  be  repeated  with  regard  to  mucous  mem- 
branes. In  this  connection,  scarlatina  is  the  most  interesting  infec- 
tion. Under  its  influence  the  streptococcus  of  the  mouth  becomes 
exalted  and  plays  an  important  part  in  the  genesis  of  early  or  tardy 
angina,  of  local  complications,  such  as  purulent  coryza.  abscess 
the  tonsils,  adenophlegmon^  of  the  neck,  or  of  complications  in 
distant  parts,  such  as  nephritis.  The  presence  of  the  streptococcus 
in  the  various  complications  observable  in  the  course  of  scarlatina 
is  so  constant  that  certain  authorities  consider  this  microbe  not  a 
superadded  agent  but  the  actual  cause  of  the  malady.  This  opinion 
is  not  yet  supported  by  absolutely  convincing  evidence.  The  case 
of  Heubner,  everywhere  cited,  who  developed  erysipelas  as  a  result 
of  having  received  in  his  face  salivary  particles  from  a  scarlatina 
patient,  demonstrates  the  exaltation  of  the  microbe,  but  by  no  means 

10 


146  IXFECTIO  US  DISEASES. 

its  specific  role.  There  exist  a  few  observations  of  patients  conva- 
lescent from  scarlatina  who  were  attacked  by  erysipelas.  The  devel- 
opment of  the  dermitis  without  any  contamination  is  another  proof 
of  the  role  played  by  the  streptococcus,  for  facts  of  this  sort,  of  which 
I  have  collected  nine  examples,  are  much  rarer  after  other  infections. 
As  there  is  no  absolute  demonstration  that  the  streptococcus  is  the 
cause  of  scarlatina,  we  may  conclude  that  this  microbe  becomes 
exalted  under  the  influence  of  an  angina,  and  thus  becomes  capable 
of  giving  rise  to  various  complications. 

Similar  considerations  may  be  presented  with  regard  to  all  affec- 
tions of  the  throat.  In  cases  of  diphtheria,  for  instance,  a  great 
number  of  microbes  are  found  in  the  false  membranes.  It  is  quite 
evident  that  there  can  be  no  pure  diphtheritic  angina.  In  order  to 
be  convinced  of  this  fact,  it  will  suffice  to  make  a  direct  examination 
of  the  false  membranes  or  to  sow  them  on  agar-agar.  Microbic  asso- 
ciations will  always  be  found.  Angina  appears  to  be  pure  only  when 
the  cultures  are  made  in  serum.  This  medium  being  more  favorable 
to  the  bacillus  of  Loeffler  than  to  other  microbes,  the  specific  agent 
is  the  first  to  develop.  Is  it  right,  however,  to  conclude  that  the 
other  bacteria  are  indifferent  because  they  vegetate  slowly  or  not 
at  all  in  this  medium  ?  The  tetragenus,  for  instance,  is  frequently 
encountered  in  anginas,  whether  diphtheritic  or  otherwise.  It  is 
seldom  noted,  because  it  develops  poorly  in  serum;  other  culture 
media  are  required.  Therefore,  the  questions  put  in  reference  to 
tetanus  and  gaseous  gangrene  may  be  asked  with  regard  to  diph- 
theria: Is  the  bacillus  of  Loeffler  capable  of  developing  alone?  Is 
it  not  rather  necessary  that  it  should  be  assisted  by  common  bacteria, 
the  common  pus  cocci  of  the  throat  which  prepare  the  soil  for  it? 

In  193  cases  of  sore  throat,  31  of  which  were  diphtheritic,  46  non- 
diphtheritic,  116  scarlatinal,  we  made  bacteriological  researches  on 
serum,  on  agar-agar,  and  by  direct  examinations.  The  results  varied 
considerably  with  the  modes  of  examination  and  the  culture  media. 
The  fact  is  that  all  microbes  have  not  the  same  aptitude  to  develop 
in  such  and  such  a  medium.  The  exclusive  presence  of  the  bacillus 
of  Loeffler  upon  a  serum  tube  simply  indicates  that  this  bacillus 
possessed  a  great  aptitude  to  vegetate  in  this  medium  and  that  its 
rapid  development  checked  and  prevented  the  multiplication  of  the 
other  bacteria.  Let  another  culture  medium  be  employed,  and  the 
results  may  be  entirely  different.  The  following  table  may  give  an 
idea  of  this  fact: 


MIOBOBIO  ASSOCIATIONS.  I  17 

SuMMun   of  Seventh  seven  Comparative  Obbebvatio      01    Seri    i 

Cim.i  LTRES    PROM    A  BTGIM  ah, 

Diphtheritic  Non-diphtheritic  ..    ,  .  _„    , 

anginas,  ■•  I  00  .  aT^tno  .  to  00 

Serum.     Agai  Serum.      Agm  vm,     Agar. 

Bacillus  of  Loeffler :;i            L8                   . .  31  16 

Streptococcus   3            L6                   25            !  -n 

Tetraoocous  5           17                  12           32  17  10 

Staphylococcus I  2  fj  5  7  7 

Pneumococcua I  *;  _'  <i 

Oidium 2  . .  I 

B.  suhlilis .  .  l  l  I               I 

Undetermined  cocci  3  2  7  2  10             4 

Undetermined  bacilli 1  2  10  L3  L5            I". 

Filaments I  ::  2 

Spirilla .  .  1  1  1               1 

From  the  mouth  mid  nasal  fossa1  microbes  may  enter  the  sinuses 
of  the  face,  the  salivary  glands,  and  the  middle  ear  by  way  of  the 
Eustachian  tube.     The  mouth  seems  to  be  even  constantly  inn 
in  certain  diseases  like  measles.     The  microbes,  however,  remain  in 
a  harmless  state  and  give  rise  to  no  disturbance. 

Combined  Infections  in  the  Respiratory  Apparatus.  Among  the 
microbes  frequently  encountered  in  the  saliva  of  healthy  individuals 
there  is  one  which,  with  the  streptococcus  and  staphylococcus,  plays 
a  very  important  part  in  the  development  of  secondary  infections — 
viz.,  the  pneumococcus.  This  microbe  often  becomes  virulent  in 
the  course  of  the  most  varied  infections  and,  notably,  in  erysipelas. 
It  may  produce  various  inflammatory  lesions  in  the  mouth.  It  must 
arrest  our  attention,  however,  on  account  of  the  complications  which 
it  may  cause  in  the  organs  of  respiration.  It  is  known  that  it  is  the 
most  frequent  agent  of  the  various  thoracic  complications  of  infec- 
tious diseases.  The  streptococcus,  its  companion  in  the  buccal 
cavity,  comes  next.  Among  the  bacteria  of  most  frequent  occur- 
rence, we  may  also  mention  the  micrococcus  tetragenus,  staphylo- 
coccus, pneumobacillus,  colon  bacillus,  etc. 

It  may  well  be  asked  how  these  germs  are  able  to  invade  the  re- 
spiratory apparatus.  The  majority  of  authors  believe  that  they  are 
driven  from  the  buccal  cavity  toward  the  lower  respiratory  passages. 
In  a  highly  interesting  work,  Dr.  Beco1  opposes  this  view.  Taking 
ground  upon  the  fact  that  pathogenic  species  are  encountered  in 
lungs  free  from  all  apparent  morphological  alteration,  and  that  these 

1  Beco.     Recherches  sur  la  flore  bacterieniie  du  poumon  de  l'homme  et  des  animaux. 
Arch,  de  m£d.  exper.,  1S99,  p.  317. 


148  INFECTIOUS  DISEASES. 

are  the  microbes  which  most  frequently  give  rise  to  bronchopulmon- 
ary infections,  he  concludes  that  the  germs  were  already  present  in 
the  lungs,  and  had  only  to  develop. 

The  argument  is  not  convincing,  however.  The  pneumococcus  has 
been  encountered  in  the  lungs,  but  the  researches  were  made  on 
cadavers.  It  is  therefore  a  question  whether  the  microbe  had  not 
penetrated  during  the  agony  or  the  ten  or  twelve  hours  which  passed 
between  the  moment  of  death  and  that  of  cultivation.  This  remark 
is  supported  by  the  fact  that  in  two  out  of  four  cases  of  sudden  death 
the  lungs  were  found  sterile.  If,  on  the  other  hand,  account  is  taken 
of  researches  pursued  on  animals,  the  conclusion  is  reached  that  the 
presence  of  the  pneumococcus  in  the  lung  is  exceptional.  We  con- 
tinue, therefore,  to  believe  that  bronchopulmonary  infections  occur- 
ring in  the  course  of  diseases  are,  as  a  rule,  due  to  buccal  germs. 
The  latter  may  be  carried  clown  with  particles  of  saliva,  or  be  dis- 
lodged by  the  current  of  air  passing  over  the  dried  mucous  membrane. 
Although  microbes  cannot  be  carried  away  by  the  inspired  air  when 
they  are  surrounded  by  fluid,  conditions  are  changed  when,  under 
the  influence  of  the  primary  disease,  the  secretions  are  scanty  and 
the  mouth  covered  with  soot. 

Whatever  may  be  the  mechanism  governing  their  development, 
the  secondary  infections  of  the  lung  are  generally  due  to  the  pneu- 
mococcus. This  is  true  in  cases  of  eruptive  fevers,  in  diphtheria, 
typhoid  fever,  and  even  in  erysipelas.  It  might  be  believed  that  in 
the  last-named  disease  the  pulmonary  complication  depended  upon 
the  streptococcus,  that  it  was  a  case  of  pulmonary  erysipelas.  Such 
was  the  old  view.  It  is,  however,  established  at  present  that  the 
streptococcus  has  no  tendency  to  leave  the  skin.  The  pulmonary 
lesion  is  the  result  of  secondary  infection,  depending  upon  the  pneu- 
mococcus. 

Combined  Infections  in  the  Alimentary  Canal.  Microbic  associa- 
tions are  likewise  constant  in  the  digestive  organs.  Experimental 
researches  have  demonstrated  their  importance  in  typhoid  fever  and 
cholera. 

With  reference  to  cholera,  the  researches  of  Metchnikoff  have  well 
shown  the  auxiliary  role  of  ingested  bacilli  and  at  the  same  time 
explained  the  resistance  of  certain  persons  and  the  immunity  of 
certain  regions.  Sanarelli  admits  an  analogous  etiology  for  yellow 
fever.  The  same  pathogenesis  may  be  claimed  for  amebic  dysen- 
tery.    Although  we  admit  the  amebse  to  be  the  specific  agents  of 


MIOBOBIO  ASSOCIATIONS.  I  19 

oik*  form  of  this  affection,  we  also  believe  thai  an  adjuvant  rdle  is 
bo  be  attributed  to  the  bacteria  thai   3warm  in  the  intestinal  ca 
and  participate  in  all  the  morbid  processes  developing  therein. 

In  most-  infections  digestive  disl urbances  appear  which  bring  aboul 
an  increased  virulence  of  microbes  colonized  iii  the  gastrointestinal 
cavity.  This  explains  the  development  of  mucomembranous  enter- 
itis consecutive  to  typhoid  fever.  Cases  of  appendicitis  have  also 
been  mentioned  as  the  result  of  the  mosl  varied  infections.  In  order 
to  resist  the  action  of  exalted  microbes,  the  lymphoid  structun 
the  appendix  become  the  seat-  of  an  inflammatory  process  which  is 
comparable  to  that  observed,  under  the  same  circumstances,  in  the 
tonsils,  and  at  times  results  in  more  or  less  profound  lesions. 

The  digestive  disturbances  may,  in  their  turn,  act  on  the  organism. 
The  toxins  elaborated  in  the  intestine  diminish  the  resistance  of 
certain  tissues  and  notably  of  the  sebaceous  glands.  Hence,  the 
frequency  of  furuncles  in  cases  of  excessive  intestinal  putrefactions. 
Both  the  old  method  of  prescribing  purges  and  the  modern  medica- 
tion by  antiseptics  act,  I  believe,  in  the  same  manner.  They  diminish 
fermentation,  and  thus  suppress  the  cause  of  secondary  infection. 

As  soon  as  the  microbes  of  the  mouth  or  of  the  intestine  become 
exalted,  they  are  capable  of  invading  the  neighboring  parts.  Sup- 
pression or  at  least  alteration  of  the  secretions  favors  the  immigration 
of  the  microbes  into  the  organs  connected  with  the  digestive  tube. 
Ancient  clinicians  had  long  remarked  that  parotiditis  occurred  par- 
ticularly in  grave  fevers  when  the  mouth  was  dry  and  repeated 
cleansing  did  not  remedy  the  absence  of  secretions.  These  glandular 
inflammations  have  become  rare  with  the  advance  of  individual 
hygiene. 

Secondary  Septicemias.  In  certain  cases  bacteria  tend  to  invade 
the  lymphatic  or  blood  channels  and  then  produce  septicemic  mani- 
festations of  a  general  character,  or  they  become  localized  in  some 
organ  and  give  rise  to  various  inflammatory  or,  oftener.  suppurative 
lesions. 

When  common  bacteria  invade  the  organism,  no  matter  what  the 
mode  of  entrance  may  be,  three  eventualities  are  possible:  (1)  In 
some  instances  the  secondary  infection  assumes  the  gravest  aspect 
and  is  expressed  by  a  septicemia  which  develops  without  determined 
localizations  and  may  rapidly  terminate  in  death.  (2)  In  other  cases 
septicemia  becomes  localized  in  some  viscus  the  disturbances  of 
which  may  be  predominant  in  the  morbid  process.    Finally,  the  germs 


1 50  IXFECTIO  US  DISEASES. 

may  at  times  be  destroyed  and  eliminated  as  fast  as  they  penetrate; 
they  may  be  found  in  the  different  secretions,  but  give  rise  to  no 
appreciable  symptom. 

There  has  recently  been  described  a  septicemic  form  of  typhoid 
fever  due  to  secondary  action  of  the  streptococcus.  This  strepto- 
typhoid  infection  (Vincent),  studied  by  Loison,  Simonin,  Arnaud, 
Vincent,  and  Wassermann,  is  characterized  by  irregularity  of  the 
fever-tracing,  very  marked  acceleration  of  the  pulse,  and  tendency 
to  hemorrhages. 

In  certain  cases  septicemia  is  expressed  by  cutaneous  eruptions. 
Rubeoliform,  scarlatiniform,  and  polymorphous  erythemata  have 
been  encountered  in  typhoid  fever.  In  two  such  cases,  Etienne  and 
Gillet  discovered  staphylococcus  in  the  blood. 

Secondary  bacteriemia  is  at  times  so  frequent  that,  without  the 
revelations  of  bacteriology,  it  would  have  been  difficult  to  determine 
its  nature.  Such  is  the  case  in  gonorrhea.  It  was  natural  to  attrib- 
ute all  the  secondary  manifestations  to  the  gonococcus  of  Neisser 
and  conclude  that  this  specific  microbe  is  capable  of  emigrating  from 
the  urethra  and  giving  rise  to  symptoms  in  distant  organs,  notably 
to  arthrites.  There  are  recorded  observations  in  which  the  joints 
contained  no  other  microbes  than  the  gonococcus.  Such  is  not 
always  the  case,  however.  It  is  not  necessarily  the  gonococcus  that 
produces  the  so-called  metastatic  phenomena.  In  many  instances 
gonorrhea  does  no  more  than  prepare  the  way  for  the  entrance  of 
the  microbes  of  suppuration,  and  what  is  found  in  the  articulations 
is  a  common  pus  coccus. 

Septicemia  may  present  a  special  aspect  when  it  occurs  at  the 
time  of  decline  of  or  convalescence  from  an  infection.  In  some  cases 
it  is  transitory,  as  primary  septicemias  sometimes  are.  It  is  even 
possible  that  certain  disturbances  of  convalescence,  which  are  too 
often  attributed  to  fatigue  or  some  error  of  diet,  are  aborted  septi- 
cemias, as  traumatic  fever  and  milk  fever  are  abortive  forms  of 
primary  septicemia. 

Septicemias  of  convalescence  are  often  attended  by  more  lasting 
manifestations,  general  disturbances,  and  cutaneous  or  visceral 
symptoms.  The  case  is  then  one  of  septicemia  with  erythema, 
purpura,  and,  in  more  serious  instances,  with  albuminuria,  gan- 
grenous lesions  of  the  skin,  etc. 

These  septicemias  may  at  times  simulate  a  secondary  complica- 
tion, notably  a  meningitis.     During  the  cholera  epidemic  of  1892  the 


MIOBOBIO  ASSOCIATIONS.  [51 

author  observed  two  cases  of  this  kind,1  and  Dr.  Siredey  has  pub- 
lished some  analogous  reports.2  The  patients  die  with  the  appearance 
of  meningeal  phenomena,  withoul  necropsy  revealing  the  slightest 

alteration  in  (he  nerve  centres  or  in  their  envelopes.     On  'he  other 

hand,  however,  bacteriology  explains  the  mechanism  of  tin-  occur- 
rences.   In  one  of  the  cases  above  referred  to,  experimenting  with 

the  cerebrospinal  fluid  and  the  liver,  the  author  obtained  pure  cul- 
tures of  an  unidentified  bacillus.  In  order  to  indicate  it-  pathogenic 
action  and  putrefactive  power,  he  called  it  bacillus  septicus  putidui . 
This  microbe  shall  be  repeatedly  referred  to  because,  on  are. Hint  of 
the  lesions  it  produces  in  animals  and  of  the  activity  of  the  toxins 
it  secretes,  it  presents  a  certain  interest  from  the  standpoint  of 
general  infectious  pathology. 

When  secondary  infections  are  somewhat  prolonged  they  may 
simulate  a  relapse.  Senger,  dwelling  on  this  point,  asserts  That,  in 
typhoid  fever,  relapses  are  often  nothing  else  than  septicemias.  The 
intestinal  ulcerations  enable  the  other  germs  to  do  mischief  which 
is  too  readily  ascribed  to  a  recrudescence  of  the  primary  disease. 
This  conception  deserves  to  be  submitted  to  rigorous  analysis,  for 
it  is  very  ingenious  and  in  harmony  with  the  actual  data  of  general 
pathology.  The  humoral  modifications  occurring  at  the  time  of 
recovery  should  prevent  relapses.  On  the  other  hand,  it  is  con- 
ceivable that  these  modified  humors  may  be  inactive  in  the  presence 
of  some  new  pathogenic  agent. 

Secondary  Localizations  of  Septicemic  Processes.  "W  hen  common 
bacteria  invade  the  organism  they  do  not  always  produce  a  general 
septicemia.  In  some  instances  they  may  become  localized  in  a 
viscus  and  give  rise  to  inflammatory  or  suppurative  disturbances. 
This  fact  raises  two  interesting  questions:  In  the  first  place,  in  the 
presence  of  an  inflamed  viscus,  the  question  is,  whether  the  lesion 
is  due  to  the  primary  process  or  to  a  secondary  one.  In  the  second 
place,  it  is  necessary  to  learn  whether  the  organ  has  been  invaded 
by  propagation  or  by  general  infection.  For  instance,  let  us  suppose 
a  suppurative  lesion  in  typhoid  fever.  Without  a  bacteriological 
analysis  it  is  impossible  to  affirm  that  it  is  a  secondary  lesion.  G. 
Roux  has  shown,  for  instance,  that  the  abscesses  in  the  spleen  may 
be  dependent  upon  the  typhoid  bacillus.     Valentini  found  no  other 

1  Roger.     Recherches  bacteriologiques  sur  un  cas  de  septicemic     See.  de  biologie. 
Oct.  29,  1S92.     Septicemic  consecutive  au  cholera.     Rev.  de  med..  Oct..  1893. 
1    Siredey.     Discussion  sur  le  cholera.     Soc.  med.  des  hop.,  Xov.  4.  1892. 


152  INFECTIOUS  DISEASES. 

than  Eberth's  bacillus  in  the  fluid  of  a  purulent  pleurisy.  Fraenkel 
made  the  same  statement  with  regard  to  a  case  of  peritonitis.  It 
has  recently  been  further  established  that  osteomyelitis  consecutive 
to  typhoid  fever  is  often  due  to  Eberth's  bacillus. 

Let  us  now  suppose  ourselves  confronted  by  an  acute  nephritis 
supervening  in  the  course  of  an  infection.  The  first  question  to  ask 
is  whether  this  nephritis  is  ascending  or  hematogenic,  viz.,  whether 
the  microbes  have  made  their  way  from  the  bladder  through  the 
ureters  or  whether  they  have  reached  the  kidney  through  the  blood- 
vessels. Pathological  anatomy,  by  discovering  the  existence  of  old 
lesions  in  the  bladder,  and  especially  by  pointing  out  the  topography 
of  the  renal  alterations,  often  enables  us  to  solve  the  first  problem. 
The  next  task  is  to  determine  whether  the  lesion  observed  is  due  to 
the  principal  microbe  or  to  a  secondary  agent.  Is  the  most  interest- 
ing of  all  infectious  nephrites,  namely,  that  of  scarlatina,  dependent 
upon  the  specific  microbe  or  upon  the  superadded  streptococcus 
which  is  constantly  found  in  the  urine  in  cases  of  scarlatinal  albu- 
minuria? 

To  sum  up,  secondary  infections,  almost  always  due  to  common 
bacteria,  are  frequently  observed  in  all  infectious  diseases.  These 
secondary  infections  may  be  expressed  by  septicemias,  symptoms 
of  which  are  confounded  with  those  of  the  principal  disease  or  which 
impart  to  the  primary  process  a  peculiar  character.  A  secondary 
infection  may  be  localized  from  the  beginning  or  subsequently  in 
one  or  several  viscera.  Hence,  a  series  of  new  manifestations  occur 
whose  nature  can  be  determined  only  by  bacteriological  researches. 

It  is  hardly  necessary  to  dwell  upon  the  importance  and  gravity 
of  secondary  infections.  Whether  septicemic  or  pyemic,  general  or 
localized,  they  may  impart  to  the  disease  a  character  of  malignancy 
by  creating  hemorrhagic  forms,  by  giving  rise  to  endocardites, 
nephrites,  degenerations  of  the  liver,  and  by  localizing  themselves  in 
arteries  and  veins.  Moreover,  they  may  render  prognosis  graver. 
If  it  is  true,  for  instance,  that  scarlatinal  nephritis  is  clue  to  a  sec- 
ondary infection,  it  is  easily  conceived  that  this  additional  infection 
is  often  graver  and  accompanied  by  more  disastrous  consequences 
than  the  primary  disease. 

Microbic  associations,  therefore,  play  a  capital  role  in  the  develop- 
ment of  diseases.  The  more  profoundly  we  study  the  pathogenesis 
of  infections  the  more  clearly  we  recognize  that  adjuvant  causes  are 
required  for  the  development  of  a  specific  microbe.     Among  these 


MIOBOBIO  ASSOCIATIONS.  \:h\ 

adjuvant  causes,  a  principal  one  i:  represented  by  the  auxiliary 
microbic  agents  vvliicli  set  the  disease  in  motion,  explain  certain 
symptoms,  and  cause  various  complications.  These  facts  do  not 
suppress  the  idea  of  specificity.     For  among  the  microbes  which 

Simultaneously  develop,  there  is  one  which  impresses  upon  the  di.-e;i~r: 

its  particular  stamp,  its  clinical  physiognomy.  The  other-  are  useful 
or  indispensable  auxiliaries,  but  do  no  more  than  add  some  features 

to  the  morbid  process. 


CHAPTER  VI. 

DEFENSES  AND  REACTIONS  OF  THE  ORGANISM. 

Means  of  Defense  of  the  Organism  against  Infections.  Role  of  the  Lymphatic  Glands 
and  Omentum.  Role  of  the  Organs,  Liver,  and  Lungs.  Variations  in  the  Action 
of  the  Liver  upon  Microbes.  Means  of  Defense  against  Microbic  Poisons.  Role 
of  the  Various  Organs;  Role  of  the  Liver.  Modes  of  Elimination  of  Microbic 
Poisons.  Reaction  of  the  Organism  against  Microbes  and  Toxins.  Mode  of 
Production  and  Signification  of  Local  Lesions.  Inflammation.  Production  of 
Inflammatory  Exudates.  Importance  of  Diapedesis  and  Phagocytosis.  Evolu- 
tion and  Reparation  of  Inflammatory  Lesions.  Mode  of  Production  and  Chemical 
Constitution  of  Serous  Exudates.  The  Fibrinous  Exudates  and  False  Mem- 
branes. 

The  Defenses  of  the  Organism  against  Infections. 

When  a  pathogenic  microbe  attacks  at  any  point  of  the  organism, 
two  events  are  possible :  First,  the  microbe  may  be  highly  virulent 
or  the  organism  in  a  weakened  state.  Consequently,  no  struggle 
takes  place,  there  being  no  resistance  on  the  part  of  the  organism. 
The  result  is  a  general  infection.  Secondly,  the  invaded  organism 
reacts  and  endeavors  to  arrest  the  invader  or  to  circumscribe  the 
infection.  A  local  reaction  is  then  produced  characterized  by  an 
afflux  of  serum  and  leucocytes.  In  some  instances  the  first  barrier 
thus  created  suffices  to  kill  the  microbe,  and  the  local  lesion  thus  saves 
the  economy. 

Unfortunately,  the  latter  is  not  always  the  case.  The  microbes 
too  often  overcome  the  first  line  of  defense  and  gain  entrance  into 
the  circulation. 

Protective  Role  of  the  Lymphatic  Glands  and  Omentum.  If  the 
microbes  pass  into  the  lymphatic  vessels  they  may  be  arrested  in 
the  lymphatic  glands.  The  interesting  researches  of  Bezancon  and 
Labbe  and  of  Manfredi  conclusively  demonstrate  the  important  role 
of  these  glands  as  defensive  organs.  This  fact  had  been  already 
indicated  by  clinical  observation.  In  the  course  of  the  most  varied 
infections,  acute,  subacute,  or  chronic  inflammations,  the  glands 
corresponding  to  the  affected  regions  swell,  and  inflammation  is  at 
times  so  intense  as  to  present  the  appearance  of  spreading  in  the 
form  of  periganglionic  edema. 


DKFFNSFS  AND  llEAOTIONB  OF  THE  ORGANISM.  \.„, 

In  spile  of  their  simple  appearance,  adenopathie  may  nun,. 
special  characters  corresponding  to  the  nature  of  the  primary  focus. 
The  glands  become  indurated  in  cases  oi  syphilitic  chancre;  they 
suppurate;  and  become  ulcerated  in  the  case  of  sofl  chancre;  they 
are  ensealed  in  tuberculosis,  etc,  However,  adenopathies .  especially 
in  their  first  stage,  must  be  considered  as  defensive  reactions.  Man- 
fred] lias  demonstrated  that  the  microbes  during  their  sojourn  in 
the  glands  lose  part  of  their  virulence,  thai  is,  they  become  atten- 
uated. 

These  considerations  regarding  I  lie  rdle  of  the  lymphatic  gland- 
lead  to  the  question  whether  other  parts  of  the  organism  similar  in 
structure  can  play  the  same  defensive  role.  Anatomists  have  come 
to  consider  the  serous  membranes  as  adne\:e  of  the  lymphatic  sys- 
tem. Let  us  consider  the  peritoneum,  for  example.1  Since  the 
investigations  of  Ranvier  the  greater  omentum  is  regarded  as  an 
extended  lymphatic  gland.  Histological  researches  have  shown 
that  the  cells  contained  in  this  portion  of  the  serous  mem- 
brane actively  proliferate  when  a  more  or  less  virulent  microbe  is 
introduced  into  the  abdominal  cavity.  When  a  moderately  virulent 
culture,  for  instance,  a  culture  of  staphylococcus  aureus,  is  injected 
.beneath  the  skin,  this  culture  gives  rise  to  extensive  suppuration; 
but  when  the  same  amount  is  introduced  into  the  peritoneum,  no 
symptoms  are  observed.  This  fact  demonstrates,  contrary  to  what 
was  once  believed,  that  a  healthy  serous  membrane  resists  infection 
better  than  does  the  subcutaneous  cellular  tissue.  It  must  be  noted, 
however,  that  the  animal  which  thus  presents  no  disturbance  shows 
some  modifications  in  the  greater  omentum,  because  the  inoculated 
microbes  pass  from  the  peritoneum  to  the  greater  omentum.  When 
small  foreign  bodies  are  introduced  into  the  peritoneum,  most  of 
them  are  gradually  pushed  by  the  intestinal  movements  toward  the 
greater  omentum  and  there  become  localized. 

It  may,  therefore,  be  concluded  that  the  greater  omentum  plays 
an  important  role  in  the  protection  of  the  peritoneum.  Experiments 
have  shown  that  its  extirpation  does  not  altogether  abolish,  but  only 
weakens,  the  resistance  of  the  peritoneum  which,  while  sufficient  to 
prevent  infection  of  the  organism  by  greatly  attenuated  microbes, 
is  no  longer  strong  enough  to  resist  virulent  microbes. 

There  are  three  defensive  barriers  opposed  to  the  exalted  microbes 

1  Roger.     Role  protecteur  du  grand  epiploon.     Soc.  de  biologie.  Feb.  19,  1S9S. 


lo6  INFECTIOUS  DISEASES. 

of  the  digestive  tract.  While  these  agents  tend  to  pass  through  the 
intestinal  walls,  they  meet  numerous  lymphoid  structures  which 
hinder  their  progress.  Should  they  overcome  this  first  line  of  de- 
fense they. may  enter  the  chyliferous  vessels,  but  they  are  then 
arrested  by  the  mesenteric  ganglia.  If  they  enter  the  portal  vein 
they  meet  the  liver,  which,  as  will  presently  be  shown,  is  capable  of 
arresting  and  destroying  them.  If  they  succeed  in  penetrating  the 
intestinal  walls,  as  is  the  case  especially  in  young  children,  they  are 
rapidly  destroyed  in  the  peritoneum,  the  protective  role  of  which 
depends  chiefly  upon  the  greater  omentum. 

Protective  Role  of  the  Liver  and  Lungs.1  When  microbes  pene- 
trate by  way  of  the  stomach  or  intestine  they  pass  into  the  portal 
vein  and  traverse  successively  the  liver,  the  right  heart,  the  lungs, 
and  the  left  heart,  to  be  thrown  thence  into  the  general  circulation. 
In  all  other  cases  they  first  encounter  the  lungs. 

Whatever  their  mode  of  penetration  may  be,  microbes  that  have 
reached  the  blood  rapidly  disappear  from  the  main  bloodvessels.  At 
the  end  of  ten  or  fifteen  minutes  they  are  no  longer  found  in  this 
location,  even  though  intravenous  inoculation  has  been  practised. 
The  blood,  then,  represents  an  inhospitable  medium  for  bacteria, 
which  must  abandon  it  and  take  refuge  in  the  capillaries  of  the  organs. 
Here  the  struggle  between  the  organism  and  the  pathogenic  agents 
is  carried  on.  The  latter  begin  to  multiply  and  secrete  toxic  sub- 
stances which  may  insure  them  victory,  while  the  cells  of  the  body 
endeavor  to  exert  their  protective  role,  either  by  producing  germicidal 
or  antitoxic  substances,  or  by  taking  up  and  digesting  the  microbes. 

Two  hypotheses  are  possible:  Firstly,  it  may  be  assumed  that  the 
various  phases  of  the  struggle  are  alike  in  all  the  capillaries.  Either 
the  microbe  or  the  organism  will  triumph,  and  the  ultimate  result 
will  be  the  sum  of  the  partial  results  of  the  same  character.  Or, 
secondly,  it  may  be  supposed  that  the  phenomena  vary  from  one 
capillary  network  to  another;  that  the  effects  of  the  struggle  are  not 
identical  in  all  the  organs,  but  in  some  of  them  the  microbe  is  victo- 
rious, in  others  the  cell.  If  so,  the  events  become  more  complex. 
The  final  result  will  be  the  sum  of  the  partial  results  of  different 
characters. 

1  Roger.  Sur  le  role  protecteur  du  foie  coutre  l'infection  charbonneuse.  Soc.  de 
biologie,  Oct.  9,  1S97.  Les  organes  protecteurs  coutre  les  infections.  Presse  med., 
June  15,  1898.  Le  role  du  foie  dans  les  infections.  Presse  m£d.,  Dec.  21,  1898.  Le  role 
protecteur  du  foie  et  du  poumon.     Cinquantenaire  de  la  soc.  de  biol.,  Dec.  27,  1899. 


DEFENSES  A  Nl>  I!  EA  <  'TIONB  <>  F  'I'll  E  <>  BO  A  NISM,  \  :,~ 

These  theoretical  considerations  lead  to  Hi''  que  'i<>n  whether 
differences  occur  in  the  evolution  <>l  infection  di  ea  e  accordii 
the  vessel  by  which  the  culture  is  introduced.  Experimenters  gen- 
erally inject  the  microbes  through  some  peripheral  vein.  The  patho- 
genic agent  then  first  pusses  through  the  capillaries  of  the  lung,  to 
subsequently  reach  the  general  circulation.  I  havethough.1  that  the 
virulent  injections  should  be  practised  through  five  differenl  chan- 
nels. 

The  author  made  inoculations  by  the  distal  end  of  the  common 
carotid  artery  in  order  to  determine  the  rdle  of  the  cerebral  capil- 
laries; by  the  distal  end  of  the  femoral  artery,  in  order  to  study  the 
influence  of  a  more  common  network  ;  by  a  branch  of  the  portal  vein, 
to  study  the  action  of  the  liver;  by  a  peripheral  vein,  to  learn  the 
role  of  the  lungs,  and,  finally,  by  the  central  end  of  the  aorta  (central 
end  of  the  carotid  artery). 

In  making  these  injections  care  should  be  taken  not  to  produce 
any  local  lesion  at  the  point  of  injection  and  not  to  use  cultures  of 
too  great  virulence.  The  evolution  of  a  local  lesion  would  confuse 
the  results,  and  the  capillary  networks  would  prove  insufficient 
barriers  against  a  culture  of  too  great  energy,  so  that  the  microbes 
would  rapidly  pass  through  them  and  produce  a  general  infection, 
evolving  in  the  same  manner,  irrespective  of  the  mode  of  entrance. 

The  microbes  employed  by  the  author  were  the  bacillus  anthracis, 
the  staphylococcus  aureus,  the  streptococcus  of  erysipelas,  the  colon 
bacillus,  and,  finally,  a  more  highly  organized  parasite,  oidium  albi- 
cans. 

The  animals  which  received  the  virus  of  anthrax  by  the  aorta 
succumbed  first.  Those  which  were  injected  through  some  periph- 
eral vein  survived  somewhat  longer,  which  indicates  a  slight  pro- 
tective action  of  the  lungs.  This  action,  however,  was  not  noticeable 
when  more  energetic  cultures  were  employed.  The  injections  prac- 
tised through  the  carotid  artery  permit  a  somewhat  longer  survival 
than  the  intravenous  inoculations.  This  result  is  interesting,  as  it 
leads  to  the  belief  that  the  nerve  centres  are  capable  of  hindering 
anthrax  infection. 

It  is  to  be  recognized,  however,  that  the  differences  observed 
according  to  the  vessel  by  which  the  anthrax  virus  is  injected  have 
so  far  been  of  little  consequence.  While  a  few  animals  resist  a  little 
longer  than  others,  all  succumb.  The  twenty  animals  which  the 
author  inoculated  through  the  aorta,  peripheral  veins,  the  femoral 


158  IXFECTIOUS  DISEASES. 

or  the  carotid  arteries,  died  at  the  end  of  a  period  varying  from 
thirty-six  to  forty-eight  hours. 

The  results  are  altogether  different  when  the  anthrax  passes 
through  the  liver.  Of  twelve  animals  which  received  considerable 
amounts  of  anthrax  culture  by  the  portal  vein,  only  three  died.  The 
liver,  therefore,  possesses  the  power  to  arrest  the  anthrax  bacilli  and 
destroy  them.  This  organ  plays  an  important  part  in  the  protection 
of  the  organism  against  anthrax  infection.  A  dose  of  £  of  a  c.cm., 
injected  by  a  peripheral  vein,  killed  a  rabbit  of  2345  grams  in 
thirty  hours,  while  a  dose  of  8  c.mm.,  introduced  bj^  a  portal  vessel, 
was  not  sufficient  to  kill  a  smaller  rabbit,  weighing  1915  grams. 
This  demonstrates  that  an  amount  of  anthrax  bacilli  sixty-four 
times  greater  than  that  which  kills  through  the  peripheral  veins 
is  completely  annihilated  by  the  liver. 

The  protective  action  of  the  liver  was  as  well  evidenced  in  experi- 
ments with  the  staphylococcus  aureus. 

The  sample  employed,  which  was  highly  virulent,  was  diluted 
with  bouillon  and  injected,  as  was  the  anthrax,  by  five  different 
vessels.  Contrary  to  the  preceding  results,  the  animals  inoculated 
by  the  distal  end  of  the  carotid  artery  succumb  first.  The  brain, 
therefore,  represents  an  excellent  culture  medium  for  the  staphylo- 
coccus. In  the  second  place,  the  animals  injected  by  the  aorta  or 
the  femoral  artery  died.  Those  which  received  the  virus  by  periph- 
eral veins  survived  longer,  and,  finally,  those  which  received  it  by 
the  portal  vein  resisted  the  inoculation. 

"When  we  come  to  the  streptococcus,  we  find  that  the  liver  exerts 
no  protective  action.  This  microbe  finds  in  the  parenchyma  of  the 
liver  excellent  conditions  for  vegetation,  and  the  animals  injected 
by  the  portal  vein  are  generally  the  first  to  succumb.  Those  which 
have  been  inoculated  by  the  aorta,  the  carotid,  or  the  femoral  artery 
die  shortly  after.  As  to  the  animals  which  have  received  the  virus 
by  the  peripheral  veins,  they  die  tardily,  or,  if  the  virus  is  not  too 
active,  they  may  survive. 

Of  the  author's  twenty  rabbits  inoculated  by  the  various  vessels, 
all  succumbed,  while  out  of  eight  animals  injected  by  the  peripheral 
veins,  three  survived. 

The  lungs,  therefore,  represent  a  protective  organ  against  the 
streptococcus.  They  play  a  role  similar  to  that  which  the  liver 
fulfils  with  regard  to  the  bacillus  anthracis  or  the  staphylococcus 
aureus.    There  is  this  to  be  noted,  however,  that  the  destruction  of 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.  159 

pathogenic  agents  by  I  lie  lunge  Li  less  active.    Tint  organ  doe*  nol 
neutralize  more  I  nan  one  fatal  d< ! 

Willi  the  colon  bacillus,  the  results  seem  somewhal  Btrange.  The 
animals  inoculated  by  the  portal  vein  or  the  carotid  artery  are  the 
first  to  succumb.  Those  which  receive  the  vim-  by  the  aorta  r< 
quite  frequently.  It  must  be  admitted,  therefore,  thai  one  of  the 
organs  tributary  to  the  arterial  system  destroys  the  microbes.  1'  is 
a  curious  fact  that  the  liver,  far  from  destroying  this  microbe,  offers 
it  an  excellent  medium  of  culture.  This  resull  explains  well  the 
frequency  and  gravity  of  hepatic  infections  of  gastrointestinal  origin. 

In  order  to  impart  a  more  general  character  to  his  researches,  the 
author  undertook  some  experiments  with  culturesof  oidium  albican,  . 
The  animals  injected  by  the  carotid  artery  axe  usually  the  firsl  to 
die.  The  lungs  very  slightly  retard  the  course  of  the  infection.  The 
liver  and  the  kidneys  arrest  great  quantities  of  the  parasites  and 
prevent  extension  of  the  process.  These  organs  very  efficiently  j »r< i- 
tect  the  economy. 

The  following  table  presents  a  resume  of  the  results  of  the  autl 
researches  on  the  protective  role  of  the  organs.     It  indicates  the 
effects  of  virulent  inoculations  and  their  variations  according  to  the 
vessels  by  which  the  cultures  are  injected: 

.,        •  Staphylococcus.    Streptococcus.     Colon  bacillus. 

r  Aorta  Carotid  artery    Portal  vein         Portal  vein 
t  very  rapid    -I  Femoral 

(.     artery  Carotid  artery    Portal  vein          Carotid  artery 

J  more  or  less  f  Peripheral  f  Aorta                    Aorta 

Death         I     rapid,  but    |       veins  Carotid  artery 

constant      ]  Carotid  1  Femoral               Femoral  artery 

[      artery  [      artery 

.inconstant              "          "  Periph'l  veins                         "         Peripheral  veins 

■  frequent  "  "  "  "        Periph'l  veins      Aorta 

Survival    <    almost  <  „     ,    .       .         „     ,    ,  ..  .,  ,. 

I  constant     {Portal  vein      Portal  vein 

Colon  bacillus  Bacillus  of  Oidium 

of  dysentery.  dysenteriform  enteritis.  albicans. 

Old  cultures        Fresh  cultures 

I  very  rapid      Portal  vein  Portal  vein  Periph'l  veins  Carotid  artery 

j  more  or  less  i  Peripheral  Portal  vein  "  "  Aorta. 

Death         J    rapid  but  -j    veins 

constant     (        "  Periph'l  veins  Periph'l  veins  Aorta 

[inconstant  "  "  "  "  "  Peripheral  veins 

.frequent  "  "  "        Portal  vein  Portal  vein 

Survival    -,  almost  Portal  vein  "  "  "  Renal  arterv 


Ve 


oust  ant 


Modifications  of  the  Action  of  the  Liver  upon  Microbes.     The 
protective  action  exercised  by  the  liver  toward  infections  seemed  to 


160  INFECTIOUS  DISEASES. 

the  author  deserving  of  complementary  researches.  It  was  of  interest 
to  learn  what  occurred  under  various  experimental  conditions.  He 
was  led  to  study  the  influence  of  fasting,  of  microbic  associations, 
and  of  certain  substances,  such  as  glucose,  sodium  bicarbonate,  and 
ether.  Excepting  one  series  in  which  an  anthrax  culture  was  em- 
ployed, staphylococcus  aureus  was  always  used. 

influence  of  Fasting.  Under  the  influence  of  fasting  the  protective 
action  of  the  liver  diminishes,  but  quite  slowly.  After  twenty-four 
hours  of  starvation  it  is  exerted  to  a  normal  degree  upon  the  anthrax 
bacillus.  If  the  inoculations  are  made  at  the  end  of  two  or  three 
days  the  antibacterial  power  is  found  to  be  weakened,  but  not  com- 
pletely suspended.  Injection  by  the  portal  vein  is  still  less  rapidly 
fatal  than  that  by  some  peripheral  veins.  This  was  demonstrated 
by  the  results  obtained  with  the  staphylococcus  aureus. 

Microbic  Associations.  We  have  already  pointed  out  that  the  effects 
of  microbic  associations  are  due  to  the  action  of  soluble  substances. 
Thus  it  is  that  sterilized  cultures  of  the  bacillus  prodigiosus  favor, 
in  a  very  marked  degree,  the  pathogenic  action  of  the  staphylococcus. 
Their  injection  by  a  branch  of  the  portal  vein  diminishes  the  pro- 
tective action  of  the  liver  and,  if  the  dose  be  sufficient,  may  even 
completely  abolish  it. 

The  fact  that,  under  the  influence  of  certain  toxins,  the  protective 
role  of  the  liver  is  abolished,  may  possibly  explain,  in  part,  the 
mechanism  of  microbic  associations,  which  is  as  yet  so  little  under- 
stood. 

The  Influence  of  Glucose.  Solutions  of  glucose  were  used  in  two 
different  ways.  In  some  cases  they  were  mixed  with  the  culture  and 
injected  into  a  branch  of  the  portal  vein.  In  other  instances  they 
were  administered  by  the  stomach.  In  the  latter  case,  its  use  was 
continued  for  two  or  three  days  in  succession. 

The  results  were  complex.  One  important  fact  is  that  the  influ- 
ence of  glucose  differs  markedly  with  the  quantity  introduced.  When 
the  sugar  is  directly  injected  into  the  blood  by  the  portal  vein,  3  to 
5  grams  suffice  to  diminish  or  suspend  the  hepatic  action.  When 
it  is  introduced  by  the  stomach,  larger  quantities  are  required. 
Sixteen  grams  exert  a  decidedly  harmful  effect,  but  not  as  great 
as  that  produced  by  the  portal  injection  of  3  grams.  Smaller 
closes,  on  the  contrary,  exert  a  stimulating  action  upon  the  liver. 
Thus,  in  one  of  the  experiments,  an  animal  which  had  received  1 
c.cm.  of  a  very  virulent  culture  through  the  vein,  and  which  ingested 


DEFENSES  AND  REACTIONS  OF  THE  ORQANU  v  Hi] 

5  grams  of  glucose  on  each  of  two  succe  ive  da;  .  urvived  even 
days,  while  the  control  died  in  eighteen  hour  . 

The  Influence   of  Bicarbonate   of  Soda.       The   author'e    expel  iment  - 

with  sodium  bicarbonate  are  ao1  very  numerous.  The  animals 
which  received  5  grams  by  Hie  portal  vein  or  io  grama  per  OS 
rapidly  succumbed  to  Hie  injection  of  relatively  Bmall  dosee  of  staph- 
ylococcus by  a  mesenteric  vein.     Ii  is  probable  thai  the  amounl  "t 

sodium  bicarbonate  injected  whs  loo  great  and,  perhaps,  by  dimin- 
ishing the  dost1,  different  resulls  would  lie  obtained. 

The  Influence  of  Ether.     The  action  of  ether  likewise  varies  wilh  the 

dosage.  The  author,  therefore,  multiplied  the  experiments.  Thirty- 
four  rabbits  served  for  these  series  of  researches.     Some  i  if  these  were 

used  as  controls;  the  others  were  treated  in  four  different  ways:  Pure 
ether  or  a  solution  of  tin"  same  was  injected  by  the  portal  veins,  or 
the  animals  were  made  to  swallow  one  of  these  fluids.  The  solution 
of  ether  was  prepared  by  agitating  ether  with  a  20  per  cent .  solution 
of  alcohol  in  water.  The  main  fact  resulting  from  these  ex]  leriments 
is  that  five  or  six  drops  of  pure  ether  introduced  by  an  intestinal 
vein  completely  abolishes  the  action  of  the  liver.  It  is  probable 
that  a  part  of  the  fluid  diffuses  and  diminishes  the  general  resist- 
ance, since  in  several  cases  the  animals  died  more  rapidly  than 
those  which  had  received  the  same  dose  by  a  peripheral  vein. 

When  the  method  of  ingestion  is  resorted  to,  it  is  found  that  doses 
of  1.5  c.cm.  of  ether  diminish  but  slightly  the  action  of  the  liver. 
In  a  dose  of  1  c.cm.  it  seems  to  augment  it.  Smaller  doses  are  best 
given  diluted.  "When  a  dilution  is  directly  injected  into  a  vein  it 
diminishes  or  abolishes  the  action  of  the  liver  in  a  dose  of  1  or  1.6 
c.cm.  By  ingestion,  greater  amounts  can  be  administered:  2  to 
3  c.cm.  of  the  solution  represent  an  excellent  therapeutic  dose  for  a 
rabbit  of  2  kilograms.  If  the  control  dies  rapidly,  death  of  the 
animal  treated  with  ether  is  delayed:  if  the  control  dies  only  after 
five  or  six  days,  the  animal  treated  generally  survives. 

In  brief,  we  conclude  from  these  researches  that  the  ingestion  of 
small  doses  of  ether  increases  the  antimicrobic  action  of  the  liver. 

All  these  experiments  were  made  with  the  staphylococcus.  The 
results  obtained  with  the  B.  anthracis  are  analogous,  although  our 
experiments  with  the  latter  microbe  are  not  numerous.  It  is  well, 
however,  to  recall  them,  as  they  confirm  the  data  already  obtained 
with  regard  to  the  slight  action  of  transitory  fasting  and  the  harmful 
influence  of  large  doses  of  ether. 

11 


162  INFECTIOUS  DISEASES. 

Defense  of  the  Organism  against  Microbic  Poisons. 

Although  the  bacteria  which  vegetate  upon  the  skin  or  in  the 
respiratory  passages  are  incapable  of  secreting  noxious  substances, 
this  is  not  the  case  with  those  swarming  in  the  digestive  tube.  It 
is  often  asserted  upon  the  dictum  of  CI.  Bernard  that  the  gastro- 
intestinal cavity  is  outside  the  organism.  In  fact,  it  is  true  that, 
in  order  to  produce  their  effects,  noxious  substances  must  pass  the 
barrier  opposed  to  them  by  the  intestinal  epithelium.  It  must,  how- 
ever, be  remembered  that  all  conditions  seem  to  combine  to  favor 
fermentations  in  the  alimentary  canal :  fermentable  materials,  abun- 
dant fluids,  and  favorable  temperature.  Therefore,  toxins  analogous 
to  those  found  in  putrefactions  are  formed,  as  may  be  demonstrated 
by  a  study  of  the  contents  of  the  intestine  or  of  the  fecal  matters. 
In  infectious  diseases,  digestive  fermentations  are  often  intensified. 
There  is  an  addition  of  poisons  formed  under  the  influence  of  patho- 
genic agents.  Although  the  organism  is  constantly  in  danger  of 
intoxication,  the  realization  is  in  most  cases  prevented  by  the  agency 
of  various  protective  systems  with  which  living  beings  are  endowed. 

Let  us  first  consider  the  substances  produced  in  the  alimentary 
canal.  Stich  asserted  that  they  are  not  absorbed.  This  greatly 
exaggerated  view  contains  a  certain  amount  of  truth.  The  interest- 
ing researches  of  Queirolo,  Denys,  Abelous,  Charrin,  and  Cassin 
establish  the  protective  role  of  the  intestinal  epithelium.  Its  cells 
act  equally  upon  vegetable  alkaloids  and  certain  microbic  toxins, 
notably  those  produced  by  the  colon  bacillus.  Poisons  which  escape 
this  first  barrier  penetrate,  in  small  amount,  by  the  lymphatic  ves- 
sels. They  are  then  arrested  and  modified  by  the  glands.  The 
greater  part,  however,  passes  into  the  blood — i.  e.,  the  portal  vein — 
and  is  thus  carried  to  the  liver. 

Action  of  the  Liver  upon  Microbic  Poisons.  The  action  of  the 
liver,  so  often  studied  and  so  well  elucidated  in  cases  of  intoxications, 
seems  far  less  clear  with  regard  to  microbic  poisons.  It  is  necessary, 
however,  to  distinguish  the  primary  poisons  from  their  derivatives. 
The  action  of  the  fiver  seems  to  be  manifest  upon  the  latter.  The 
author  recognized  this  fact  as  early  as  1887,  when  studying  the 
putrid  poisons.  The  results  of  these  experiments,  reducing  to  kilo- 
gram of  animal  the  quantities  of  extract  of  tissues  injected,  are 
summed  up  in  the  following  table: 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.  103 

Quantity  introduced. 
Do 

Fluid  injected.                      Inimal  experimented.              Non-fatal      Fatal 
Dialized  extrad  .      .      .     J  Healthy  frog 300 

i  l  rofl  -.mi I, ..in  b  lii  er,      .      .  300 

Ethered  extrad  -      ,      ,     [H<  alth; 837 

I  Frog  without  a  liver 837 

I  Rabbil  'i"  i iph<  ral  vein).      .      .  91 

Alcoholic  ex1  racl  .    ■        "       [portal  vein) ,      .      .      .      I  <  l 

'        "       (portal  vein) 216 

It  will  suffice  to  remark  thai  in  the  experiments  upon  the  rabbil 
the  relation  of  fatal  doses,  according  as  the  injection  ia  given  by  .•> 
peripheral  vein  or  some  branch  of  the  portal  vein,  is  ae  2.36  to  I. 
It  is,  therefore,  permissible  to  conclude  thai  the  liver  arreste  <■<  rtain 
toxins  extracted  from  putrid  substances  in  the  same  manner 
arrests  vegetable  alkaloids.  It.  can  also  acl  upon  various  bodies 
which  often  originate  under  the  influence  of  microbes.  Thus,accord- 
ing  to  Kochs,  it  shares  with  the  kidneys  the  property  of  presiding 
over  the  modification  of  aromatic  substances,  and  il  ia  known  thai 
aromatic  substances,  notably  phenol,  thus  lose  much  of  their  noxious 
power. 

Microbes  also  give  rise  to  the  formation  of  ammonia,  and  the  liver 
again  comes  to  the  assistance  of  the  organism  by  arresting  and  neu- 
tralizing the  ammonium  salts,  those  at  least  in  which  the  base  is 
united  with  carbonic  acid  or  some  organic  acid. 

The  study  of  putrid  substances  is  particularly  interesting  because 
of  the  deductions  that  may  be  drawn  for  the  history  of  intestinal 
fermentations.  The  substances  originating  in  the  digestive  tube  are, 
in  fact,  analogous  to  putrid  substances,  and  the  liver  also  acts  upon 
these  poisons. 

The  researches  of  Drs.  Teissier  and  Guinard1  have  led  to  the  unex- 
pected conclusion  that  the  liver  exerts  no  protective  action  against 
the  toxins  of  diphtheria  and  of  pneumobacillus.  Xot  infrequently, 
especially  in  the  dog,  the  action  of  the  poison  is  more  energetic  when 
it  passes  through  the  liver. 

These  results  should  not,  however,  be  hastily  generalized.  The 
toxin  of  the  dysenteric  colon  bacillus  is  neutralized  by  the  liver. 
AYhile  0.5  com.  injected  into  the  peripheral  veins  of  a  rabbit  kills 
this  animal  in  two  or  three  days,  an  amount  four  times  greater  intro- 
duced by  the  portal  vein  causes  simply  diarrhea.     If  greater  quan- 

1  Teissier  et  Guinard.  Rccherehes  experimentales  sux  les  effets  des  Toxines  micrc- 
biennes  et  sur  quelques  influences  capables  de  les  modifier.  Arch,  de  med.  exper..  lv"7. 
p.  994. 


1(34  INFECTIOUS  DISEASES. 

tities  are  administered,  the  liver  is  no  longer  capable  of  saving  the 
animal,  but  prolongs  its  existence.  Twenty  cubic  centimetres  of  a 
slightly  weakened  culture  were  injected  into  two  rabbits.  One, 
weighing  1S25  grams,  received  the  fluid  by  a  peripheral  vein,  and 
died  in  collapse  at  the  end  of  seven  hours  and  a  half;  the  other 
animal,  weighing  1S15  grams,  received  the  poison  by  the  portal 
vein,  and  died  at  the  end  of  four  days. 

Action  of  the  Various  Organs  upon  Microbic  Poisons.  Recent 
researches  establish  that  the  lungs  are  able  to  attenuate  the  action 
of  certain  poisons.  They  act  upon  vegetable  alkaloids  and  sub- 
stances such  as  ammonium  carbonate  and  fatty  acids,  which  may  be 
produced  under  the  influence  of  certain  microbes.  However,  its 
influence  upon  toxins,  at  least  upon  the  diphtheritic  toxin,  seems  to 
be  nil.  Animals  comparatively  inoculated  by  the  carotid  artery  and 
the  jugular  vein  die  within  the  same  period  of  time.  The  artificial 
circulation  of  the  toxin  through  the  lungs,  even  when  prolonged  for 
nearly  an  hour,  in  nowise  modifies  its  action.  No  general  conclusion 
should  be  drawn  from  this  negative  result,  which  must  lead  only  to 
further  investigations.  It  should  be  equally  interesting  to  study 
the  action  which  other  parts  of  the  organism — the  spleen,  the  thyroid 
gland,  the  suprarenal  capsules,  the  bone-marrow,  the  thymus,  etc. 
— may  exercise  upon  toxins.  All  that  we  know,  since  the  remark- 
able experiment  of  Wassermann  and  Takaki,  is  that  the  brain  pos- 
sesses the  power  to  fix  and  aniiihilate  the  toxin  of  tetanus. 

Modes  of  Elimination  of  Toxins.  As  soon  as  microbic  toxins  enter 
the  blood  they  probably  undergo  attenuation  by  oxidation  or  by 
neutralization  exercised  through  certain  principles  which  the  leuco- 
cytes diffuse.  As  already  stated,  the  kidneys  also  serve  for  the 
elimination  of  toxins.  It  may,  however,  be  a  question  whether 
they  simply  excrete  the  circulating  poisons  or  whether  they  pre- 
viously submit  them  to  some  analysis.  As  a  matter  of  fact,  it  has 
been  demonstrated  that  infectious  poisons  contained  in  the  organism 
are  albuminoid  substances.  Those  contained  in  the  urine  are  of  an 
alkaloid  nature  and,  unlike  the  former,  resist  higher  temperatures 
fairly  well.  It  may,  therefore,  be  asked  whether  the  primary  com- 
plex molecule  is  not  broken  up  in  the  kidneys  and  does  not  leave 
in  these  organs  its  alkaloidal  radical.  This  is  no  more  than  an 
hypothesis,  but  is  worthy  of  verification.  The  remark  might  even  be 
extended  to  autointoxications.  In  the  course  of  uremia,  the  poisons 
contained  in  the  blood  and  organs  are  likewise  of  an  albuminoid 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.         ]<;:> 

nature,  while  the  urinary  poison  is  not  an  albumin.     El  may,  tl 
fore,  be  supposed  that  the  kidneys  possess  the  power  of  breaking 
the  complex  molecules  of  the  products  of  di  at  imilation.     In  this 
manner,  better  perhaps  than  by  an  internal    ecretion,  may  be 
explained  those  cases  of  uremia  which  occur  when  the  permeability 
of  the  kidneys  is  but  slightly  modified. 

There  are  other  modes  of  depuration.  The  respiratory  apparatus 
eliminates  volatile  substances,  probably  the  leasl  importanl  ones, 
some  of  them  chemically  defined.  They  imparl  to  the  breath  the 
disagreeable  odor  observed  in  various  infections,  notably  in  those 
attended  by  increased  intestinal  putrefactions.  The  skin,  likewise, 
may  eliminate  toxins,  and,  like  the  lungs,  throws  ou1  volatile  sub- 
stances, among  which  sulphuretted  hydrogen,  ammonia,  fatty  acids, 
and  acetone  occupy  the  first  rank.  It  may  also  eliminate  a  certain 
amount  of  noxious  substances  with  the  perspiration.  We  are  not, 
however,  well  informed  upon  this  point,  and  accurate  experiments 
are  lacking.  It  is  well  to  remember  that  subcutaneous  injections 
of  pilocarpine  often  produce  an  improvement  in  the  general  state 
of  patients  suffering  from  diphtheria.  It  would  be  interesting  to 
inquire  into  the  properties  of  the  increased  perspiration  secreted  under 
these  conditions.  The  eliminating  role  of  the  bile  and  gastrointes- 
tinal secretion  is  not  any  more  clearly  understood.  The  frequency 
of  diarrhea  and  vomiting  in  animals  which  have  received  microbic 
toxins  tends  to  demonstrate  the  existence  of  elimination  through  the 
alimentary  canal.  This  hypothesis,  to  which  occurrences  in  certain 
cases  of  poisonings  also  point,  finds  an  additional  support  in  the 
researches  pursued  by  the  author  upon  the  toxins  of  the  colon  bacillus 
of  dysentery.  When  the  toxin  was  prepared  with  a  sample  of  mod- 
erate virulence  and  was  relatively  weak,  its  introduction  caused  pro- 
fuse diarrhea.  When  it  was  derived  from  a  highly  virulent  sample, 
its  action  was  more  powerful,  but  there  was  very  little,  if  any, 
intestinal  flux. 

Our  knowledge  concerning  the  passage  of  toxins  into  the  milk  is 
far  from  complete.  A  few  observations,  notably  those  reported  by 
Sevestre,  Lesage.  and  Siebert,  tend  to  prove  that  the  use  of  tainted 
foods  may  cause  diarrhea  in  the  mother  and  the  nursling.  In  a  case 
mentioned  by  Lesage  the  child,  seven  months  old,  died  in  forty-eight 
hours  with  symptoms  of  infantile  cholera.  Facts  have  been  pub- 
lished demonstrating  that  even  a  benign  intercurrent  infection  may 
impart  to  the  milk  a  certain  degree  of  toxicity  and  give  rise  to  various 


166  IXFECTIO  US  DISEASES. 

manifestations  and  particularly  to  diarrhea  in  the  child.  This  has 
been  observed  in  a  case  of  phlegmonous  tonsillitis  (Henoch)  and  of 
vaccinia  (Marfan).  The  experiments  of  Brieger  and  Ehrlich  demon- 
strated that  the  toxins  of  diphtheria,  tetanus,  and  typhoid  fever  pass 
into  the  milk.  According  to  Pasquale  and  Michele,  the  same  is  true 
of  those  of  tuberculosis.  It  must  be  remarked,  however,  that  though 
the  milk  of  sick  women  is  at  times  contaminated,  it  may,  in  the 
majority  of  cases,  be  ingested  without  any  inconvenience.  In  the 
writer's  hospital  wards  he  allows  the  mothers  to  nurse  their  infants 
when  the  infection  from  which  they  suffer  is  to  be  of  short  duration. 
A  great  number  of  women  suffering  from  measles,  scarlatina,  mumps, 
erysipelas,  sore  throat,  or  even  diphtheria,  have  continued  to  nurse 
without  any  harmful  results  for  the  nurslings.  It  has  been  necessary, 
in  most  cases,  only  to  supplement  the  diminished  secretion  of  the 
mother's  milk  by  artificial  feeding.  As  soon,  however,  as  deferves- 
cence took  place,  the  secretion  was  re-established.  The  author  was 
inspired  to  this  practice  by  the  desire  to  avoid  weaning  the  children 
definitely,  since  the  effects  of  artificial  feeding,  especially  among  the 
poor  classes,  are  only  too  well  known. 

The  Reactions  of  the  Organism  against  Infections. 

Role  and  Signification  of  Local  Lesions.  Disease  is  the  result  of 
two  contrary  actions :  In  the  first  place,  there  is  an  attack  of  some 
pathogenic  agent  upon  the  organism.  In  the  second  place,  a  series 
of  reactions  calculated  to  hinder  or  neutralize  the  morbid  effects 
occur. 

To  take  a  very  simple  example,  let  us  suppose  a  pyogenic  coccus 
to  have  been  deposited  beneath  the  skin.  This  microbe,  finding  in 
the  interstitial  fluids  of  the  tissue  conditions  favorable  for  its  devel- 
opment, rapidly  multiplies.  If  it  behaved  like  a  simple  inert  body, 
it  might  form  large  colonies  without  producing  any  appreciable 
reaction  on  the  part  of  the  organism.  Not  so,  however.  The  microbe 
elaborates  soluble  substances,  some  of  which  alter  the  surrounding 
tissues,  and  others,  carried  by  the  circulation,  directly  influence  the 
entire  organism.  Reactions  on  the  part  of  the  organism  are  then 
aroused.  If  the  substances  elaborated  by  the  microbe  are  very 
active  they  cause  immediate  death  of  the  cells  with  which  they  come 
in  contact.  If  less  energetic,  they  give  rise  to  an  irritation  which 
is  expressed  by  responsive  phenomena  occurring  in  the  cell    and 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.  [67 

without  any  intervention  of  the  nervous  system  or  the  circulation. 
At  the  same  time,  the  microbic  substances  and  the  products  elabo- 
rated by  the  altered  cells  excite  the  surrounding  vessel  and  especially 
the  nerve  terminations.  By  this  mechanism  a  series  of  new  morbid 
manifestations  is  produced,  some  of  which,  of  a  true  reflex  nature, 
return  to  the  starting  poiul  of  excital  ion,  while  other  extend  to  the 
most  distant  parts  of  I  lie  organism, 

Even  when  the  lesion  remains  local  and  the  toxins  do  not  pene- 
trate (lie  economy  Hie  nervous  system  which,  under  normal  condi- 
tions, assures  functional  synergy,  suffices,  under  pathological  condi- 
tions, to  give  rise  to  a  series  of  morbid  sympathies.  However,  toxins 
are  almost  always  absorbed  and,  at  points  at  which  they  reach  the 
cells,  they  induce  manifestations  identical  with  those  which  occur 
at  the  point  primarily  invaded,  viz.,  irritation  of  the  cells,  cellular 
reactions,  excitation  of  bloodvessels  and  nerve  terminations,  reflex 
to  the  point  of  origin  and  reflex  to  distant  parts.  Finally,  in  a  great 
number  of  instances,  the  figurate  elements  also  penetrate  the  econ- 
omy, settle  at  certain  points,  elaborate  toxins,  and  the  series 
manifestations  just  described  immediately  recur. 

If  we  consider  the  point  primarily  attacked  by  a  microbe  which  has 
been  deposited  beneath  the  skin,  for  example,  we  see  that  at  the 
point  of  its  introduction  a  series  of  manifestations  develop,  resulting 
in  the  production  of  a  local  lesion.  The  latter  represents  a  true 
barrier  opposed  to  the  invasion  of  the  pathogenic  agent.  It  is 
absent  under  two  quite  different  circumstances.  If  the  microbes 
meet  an  organism  endowed  with  perfect  immunity,  the  interstitial 
fluids  exert  a  germicidal  action  upon  them  and  prevent  their  devel- 
opment. A  certain  number  of  them  are  killed  and  the  action  of  the 
others  is  inhibited  to  such  a  degree  as  to  allow  the  leucocytes  to 
completely  eliminate  them  from  the  economy.  In  this  instance  the 
local  lesion  is  not  produced,  because  it  would  be  of  no  use.  The 
organism  is  so  resistant  that  the  invader  is  destroyed  without  any 
apparent  struggle.  Even  in  such  cases,  however,  the  destruction  of 
bacteria  is  not  as  speedy  as  might  appear  at  first  sight.  Certain 
non-pathogenic  bacteria,  especially  if  they  are  sporulated,  may  sur- 
vive for  a  very  long  period  of  time.  They  remain  as  harmless  foreign 
bodies,  and  behave  altogether  like  insoluble  substances.  It  is  likely 
that  they  give  rise  to  no  defensive  reaction  because  they  are  devoid 
of  irritant  secretions. 

When  the  microbe  is  highly  pathogenic  or  the  organism  non- 


168  INFECTIOUS  DISEASES. 

resistant  the  local  lesion  is  likewise  wanting,  although  for  quite 
different  reasons.  The  fluids  then  exercise  no  germicidal  power,  the 
microbe  rapidly  develops  and,  at  the  same  time,  secretes  toxins,  some 
of  which,  being  absorbed,  paralyze  the  nerve  centres  and  prevent 
vasodilatation  preparatory  to  serious  exudation  and  diapedesis. 
Others  exercise  a  negative  chemotactic  action,  viz.,  repel  the  few 
phagocytes  which  approach  the  infected  focus. 

In  cases  in  which  the  invading  microbe  is  virulent  the  local  lesion 
represents  a  salutary  reaction.  This  reaction,  however,  like  all  other 
reactions,  may  become  a  new  source  of  danger.  A  microbe  which 
is  implanted  in  a  mucous  membrane  is  capable  of  causing  very 
serious  accidents :  for  example,  in  the  larynx,  edema  of  the  glottis  ; 
in  the  lungs,  foci  of  fibrinous  pneumonia  and  bronchopneumonia, 
which,  by  their  extent,  may  prove  fatal. 

On  the  other  hand,  the  effect  may  exceed  the  end.  The  organism 
at  times  mobilizes  all  its  reserves  upon  slight  alarm,  and  thus  creates 
useless  lesions.  The  congestion  which  surrounds  a  circumscribed 
pulmonary  lesion  must  often  be  combated.  The  same  is  true  with 
regard  to  diarrhea  and  effusions  in  serous  membranes  which  some- 
times reach  considerable  amounts  in  disproportion  to  the  slight 
morbid  cause  that  gives  rise  to  all  these  effects.  An  interesting 
experiment  of  Gamaleia  shows  how  excessive  and  dangerous  organic 
reactions  may  sometimes  become.  This  author  produced  in  two 
rabbits  a  chemical  irritation  of  the  cornea.  In  one,  reaction  was 
allowed  to  follow  its  natural  course,  and  terminated  in  an  opacity. 
In  the  other  case,  the  reaction  was  checked  by  various  procedures 
which  prevented  the  reflex  congestion  of  the  neighboring  parts,  and 
the  cornea  remained  transparent. 

The  practical  importance  of  these  pathogenic  data  is  readily  con- 
ceived. Since  therapeutics  furnishes  us  with  means  capable  of 
intensifying  or  attenuating  reactionary  phenomena,  it  is  the  duty 
of  the  clinician  to  determine  the  conditions  under  which  the  inflam- 
matory reaction  is  produced,  to  recognize  whether  it  is  useful,  insuf- 
ficient, or  excessive,  and  to  respect,  intensify,  or  moderate  it  accord- 
ingly. 

Inflammatory  Reactions.  Whether  or  not  a  local  lesion  exists, 
microbes  may  invade  the  economy  and  settle  in  tissues  and  organs. 
In  other  cases  they  remain  localized  at  the  point  of  introduction, 
but  secrete  substances  which  diffuse  and  impregnate  the  economy. 
In  both  instances,  visceral  foci  develop  which,  in  their  turn,  become 


DEFENSES  AND  REACTIONS  OF  THE  OBQ  i  VI8M.  169 

the  starting  point  of  morbid  reactions.    The  e  reactionary  phenom- 
ena are  known  under  the  name  of  inflammation, 

No  term  is  oftener  employed  in  medicine,  and  none,  perhaps,  hag 
a  meaning  as  much  lacking  in  precision   at  the  word  inflammation. 

Discarding  the  ancient  theories,  which  are  merely  of  historical 
interest,  we  find,  a1  the  presenl  epoch,  al  leasl  three  differenl  con- 
ceptions of  the  process  in  quesl  ion :  I .  Thai  of  Virchow,  according  i<> 
which  inflammation  is  characterized  essentially  by  cellular  alterations, 
the  vascular  phenomena  being  of  secondary  importance.  2.  Thai 
of  Cohnheim,  who  sees  in  inflammation  the  sum  of  proa  which 
begin  by  vascular  dilatation  and  resull  in  transudation  and  diape- 
dosis  (migration).  8.  Thai  of  Mctchnikoff,  who  defines  inflammation 
as  ;i  salutary  reaction  tending  to  check  infection  by  phagocytosis. 

Whosoever,  independently  of  theoretical  discissions,  looks  for  a 
characteristic  of  inllannna.tion  will  see  that  this  term  must  retain  a 
very  comprehensive  meaning.  As  the  question  here  concern-  infec- 
tious diseases,  we  shall  define  inflammation  as  "the  ensemble  of 
reactionary  phenomena  produced  at  the  points  irritated  by  microbic 
toxins." 

These  phenomena  are  multitudinous  and  may  be  classified  as 
follows: 

Alteration  of  fixed  cells. 
Reflex  vascular  disturbances. 
Exudation  and  diapedesis. 

Though  not  the  first  by  order  of  occurrence,  vascular  disorders  are 
first  observed.  They  are  easily  appreciable,  and  the  patient  himself 
may  notice  them  by  the  intensity  of  painful  pulsations  which  he 
experiences.  The  clinician  as  well  as  the  anatomist  detects  them 
without  difficulty.  It  has,  therefore,  been  asserted  that  congestion 
is  the  first  stage  of  inflammation.  As  a  matter  of  fact,  it  is  preceded 
by  a  local  change  in  nutrition.  It  is  readily  understood  that,  in 
reality,  the  presence  of  microbic  poison  modifies  the  medium  which 
surrounds  the  cells,  and,  as  life  is  an  adaptation  of  the  cells  to  the 
medium,  when  the  latter  changes  the  cells  also  must  be  modified. 
Their  nutrition  and.  consequently,  their  activity  cannot  remain  what 
they  previously  had  been.  There  will  first  occur  a  dynamic  change 
in  the  cell,  which  change  will  bring  in  its  train  further  histochemical 
modifications.  A  lesion  appreciable  under  the  microscope  may  soon 
be  detected,  but  it  certainly  is  not  the  primary  lesion.  It  is  the 
result  of  a  previous  disturbance  in  cell  function. 


170  INFECTIOUS  DISEASES. 

The  excitation  of  nerve  terminations  by  microbic  toxins  and  by 
the  products  secreted  by  the  already  modified  cells  produces  an 
active  reflex  vasodilatation  at  the  point  attacked.  It  is  readily  con- 
ceived that  the  more  excitable  the  nervous  system  the  earlier  will 
congestion  set  in  and,  consequently,  the  more  acute  the  process  will 
be;  that  is  to  say,  the  greater  will  be  the  chances  of  a  favorable 
evolution.  A  very  simple  experiment  confirms  this  hypothesis. 
After  the  sensory  nerves  of  a  rabbit  have  been  sectioned  at  the  base 
of  the  ear,  it  is  noticed  that  the  subcutaneous  inoculation  of  the 
streptococcus  produces  far  graver  lesions  than  in  the  intact  ear. 

According  to  the  qualities  of  the  pathogenic  agent  and  the  respon- 
sive aptitude  of  the  organism,  congestion  may  be  effected  in  a  slow 
and  progressive  manner  or  rapidly,  almost  suddenly.  In  the  latter 
case,  if  an  important  organ  is  invaded,  disturbances  may  suddenly 
become  manifest.  Everyone  is  acquainted  with  the  violent  pain 
and  dyspnea  attending  acute  congestion  of  the  lungs. 

Preceding  and  explaining  serous  exudations  and  cliapedesis,  acute 
congestion  represents  the  first  stage  of  inflammatory  reaction.  It  is 
the  beginning  of  a  defensive  act.  Therefore,  whenever  reaction  is 
tardy  or  weak  we  must  stimulate  the  process.  Three  procedures, 
practised  upon  animals,  enable  us  to  obtain  this  result,  and  all  three, 
by  stimulating  inflammatory  reactions,  favor  healing  of  the  lesions. 
First,  section  of  the  sympathetic,  the  influence  of  which  upon  the 
course  of  experimental  erysipelas  has  been  shown  (Roger).  Secondly, 
heat,  by  the  agency  of  hot  water  circulating  about  the  affected  parts 
(Filhene).  Therapeutics  demonstrates  the  same  favorable  influence 
of  hot  applications  in  the  treatment  of  erysipelas,  and  popular  tradi- 
tion has  long  taught  us  that  a  paronychia  may  be  cured  by  plunging 
the  finger  in  almost  boiling  water.  In  this  case  the  temperature  is 
not  sufficiently  raised  to  kill  the  microbe;  the  action  is  indirect 
through  the  congestion  thus  produced.  Finally,  as  Dr.  Carnot  has 
pointed  out,  analogous  results  are  obtained  by  submitting  the  inocu- 
lated animals  to  the  influence  of  vasodilating  substances,  such  as 
amyl  nitrite. 

Acute  vasodilatation  of  the  affected  region  is  expressed  by  increased 
afflux  of  arterial  blood  and,  consequently,  acceleration  of  the  circu- 
lation. The  blood  remains  red  in  the  veins.  This  result  is  impor- 
tant, as  the  leucocytes  cannot  leave  the  vessels  except  when  the 
supply  of  oxygen  is  considerable.  If  the  veins  are  compressed  so  as 
to  slow  the  blood  current,  migration  no  longer  takes  place. 


DEFENSES  ANh  REACTIONS  OF  THE  OROA  VJSM.  17] 

The  exodus  of  leucocytes  is  preceded  by  an  intermediate 
■second  stage  of  inflammation  characterized  by  a  lowing  of  the 
blood  current.  Then  there  occur  whal  Cohnheim  bag  described  as 
"marginatum"  of  the  leucocytes.  These  cells  areseen  to  adhere  to 
the  wnl Is  of  the  veins,  while  in  the  capillaries  they  remain  mixed  with 
the  red  corpuscles. 

Then  begins  the  third  Btage,  characterized  by  two  events  of  prime 
importance,  migration  and  exudation. 

The  leucocytes  puss  ou1  of  the  smaller  veins  and  capillaries.  Those 
passing  out  through  the  hitler  route  lenvc  behind  them  small  aper- 
tures through  which  a  few  red  corpuscles  may  also  escape.  Nol  all 
leucocytes,  however,  are  of  the  migratory  variety.  The  lymphocytes 
are  but  slightly  motile.  The  eosinophils  are  endowed  with  sluggish 
motion.  It  is  especially  the  varieties  known  as  mononuclear  and 
polynuclear  neUtrophiles  that  take  the  greatest  part  in  the  pr< 
and  are  particularly  charged  with  the  task  of  incorporating  and 
digesting  the  microbes. 

Coincidently  with  this  migration  there  occurs  a  more  or  less  abun- 
dant exudation  consisting  of  a  serous  or  serofibrinous  fluid. 

It  is  difficult  to  gain  an  insight  into  the  mechanism  of  exudation. 
The  mechanical  explanation,  at  first  accepted,  is  daily  losing  ground. 
It  is  admitted  that  venous  stasis  cannot  account  for  the  process  and 
that  ascites  as  well  as  hydrothorax  and  hydrocele  must  be  attributed 
to  a  subacute  or  chronic  inflammation  of  the  peritoneum,  pleura,  or 
the  tunica  vaginalis,  respectively.  This  view  may  be  supported  by  the 
well-known  experiments  of  Ranvier  and  those  pursued  by  the  author 
with  Dr.  Josue.1  They  have  shown  that  ligature  of  the  three  efferent 
veins  of  the  pinna  of  the  ear  is  not  followed  by  an  effusion  into  the 
cellular  tissue  of  the  organ;  but  if  at  the  same  time  the  superior 
cervical  ganglion  of  the  sympathetic  is  excised,  or  if  a  few  dro]  - 
a  sterilized  culture  of  bacillus  proteus  is  injected,  edema  appears 
and  persists  for  several  days. 

The  inadequacy  of  the  mechanical  theory  is  further  shown  by  the 
fact  that  the  transuded  fluid  does  not  possess  the  same  constitution 
as  the  blood  plasma.  The  amount  of  salts  is  the  same;  but  not  so 
when  the  organic  materials  are  considered,  which  seem  to  be  fur- 
nished in  a  selective  manner,  as  a  true  secretion. 

When  once  out  of  the  bloodvessels,  the  leucocytes  proceed  toward 
the  points  occupied  by  the  microbes,  and  attack  them.     There  has 

1  Roger  et  Josue.    Xote  sur  la  pathogenie  de  I'oedeme.    Soc.  de  biologie.  July  27   1  - 


172  INFECTIOUS  DISEASES. 

been  much  discussion  in  reference  to  the  wonderful  faculty  with 
which  they  are  said  to  be  endowed  or  the  kind  of  instinct  they 
display.  Recent  researches  demonstrate  that  the  process  is  one 
embraced  by  a  law  of  general  biology.  It  is  a  phenomenon  first 
studied  by  naturalists,  and  which  PfeifTer  has  described  under  the 
name  chemotaxis,  and  of  which  Pekelharing  and  especially  Bordet 
and  Massard  have  shown  the  importance  in  animal  pathology. 

The  soluble  substances  maybe  divided  into  three  groups,  according 
as  they  attract,  repel,  or  exert  no  action  whatever  upon  the  leuco- 
cytes. 

The  majority  of  microbic  products,  and  notably  those  of  staphy- 
lococcus aureus,  attract  the  migratory  cells.  The  waste  products 
of  the  cells  of  the  economy  do  the  same,  a  fact  of  the  greatest  con- 
sequence, since,  from  the  very  beginning  and  during  the  entire  course 
of  infection,  microbes  secrete  substances  which  alter  or  kill  the  cells. 
On  the  contrary,  the  bacillus  of  chicken  cholera  exercises  a  negative 
chemotactic  action,  viz.,  it  repels  the  leucocytes,  at  least  those  of 
the  rabbit.     Hence,  the  facility  of  microbic  generalization. 

The  round  cells  which  are  found  in  an  inflammatory  exudate  are 
not  all  derived  from  the  blood.  A  certain  number  of  them  are  fur- 
nished b}^  the  fixed  cells  of  the  connective  tissue.  In  this  connection 
the  most  interesting  modifications  are  those  of  the  giant  elements 
described  by  Ranvier  under  the  name  clasmatocytes. 

The  fat  of  the  adipose  cells  disappears  and  the  elements  resume  a 
younger  form.  The  endothelia  likewise  tumefy  and  return  to  their 
embryonal  shape.  In  a  word,  the  cells  of  mesodermic  origin  resume 
the  functions  which  they  exercised  during  the  embryonal  period. 
They  recover  their  contractility  and  motility.  This  law  seems  to 
be  applicable  even  to  the  muscular  fibres.  In  this  instance,  however,, 
more  highly  organized  and,  consequently,  more  sensitive  elements 
are  concerned.  Therefore,  the  process  of  degeneration  prevails  over 
the  reactionary  phenomena. 

In  the  midst  of  these  profound  modifications  the  epithelial  cells 
do  not  remain  intact.  If  the  toxins  are  not  very  noxious  the  modi- 
fication of  the  medium  excites  an  increased  activity  on  the  part  of 
the  cellular  element,  and  the  phenomena  of  proliferation  and  notably 
karyokinetic  figures  occur.  "When,  on  the  contrary,  the  toxins  are 
highly  energetic,  the  exchanges  between  the  adulterated  medium  and 
the  epithelial  cells  cause  a  series  of  functional  disturbances  which 
soon  result  in  structural  modifications.     The  cell  may  be  killed  at 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.  17-; 

I  he  outest.  H.  undergoes  a  particular  fermentation  which  tran  forms 
[t  into  a  homogeneous  mass  resembling  fibrin.  This  is  known  at 
coagulation  necrosis.  In  case  theelemenl  is  still  capable  of  reacting 
it  presents  the  scries  of  lesions  which  have  been  described  a  granular, 
pigmentary,  hyaline,  colloid  or  mucous,  vitreous,  ca  eous  degenera- 
tion, and  the  like.  It  may  be  stated  that,  as  a  rule,  degeneration 
occurs  more  frequently  and  earlier  in  epithelia  than  in  connective 
tissue  cells,  for  I  he  re: i son  thai  the  structure  of  the  former  is  more  deli- 
cate and  renders  them  more  sensitive  to  various  morbific  influences. 

The  changes  in  the  structure  of  cells  revealed  by  the  microscope 
result,  as  already  stated,  from  functional  disorder  caused  by  modi- 
fications of  the  medium.  II  musi  be  noted,  however,  thai  the  nutri- 
tional disturbances  in  their  turn  influence  the  function-  of  the  cells 
and  notably  their  secretory  activity.  In  cases  of  slight  inflamma- 
tion the  cells  react  with  energy,  and  their  secretions  are  more  abun- 
dant than  under  normal  conditions.  It  will  suffice  to  recall  the 
intense  salivation  occurring  in  angina,  the  nasal  flow  in  coryza, 
bronchial  hypersecretion  in  inflammations  of  the  respiratory 
sages,  the  diarrhea  in  enteritis,  etc.  When  the  process  is  violent, 
the  reverse  is  observed.  Secretions  dry  up:  the  tongue,  the  throat, 
the  skin  are  dry,  and  urine  is  scanty 

According  to  the  nature  or  intensity  of  the  process,  the  aspect  of 
the  inflammatory  focus  varies  considerably.  In  its  simplest  expres- 
sion the  lesion  consists  of  a  serous  exudate.  In  a  higher  degree,  the 
fibrin  coagulates,  pseudomembranous  deposits  appear,  and  exudates 
are  formed.  If  the  toxins  cause  the  death  of  a  certain  number  of 
cells,  the  exudate  undergoes  a  purulent  transformation.  In  other 
instances  bacteria  produce  therein  fermentations  similar  to  those 
characterizing  putrefactions.  The  result  is  then  a  putrid  effusion 
or  a  gangrene,  according  as  the  process  occurs  in  the  exudated  fluid 
or  in  the  tissue  itself. 

When  the  round  cells  are  very  abundant  they  are  either  scattered 
or  form  nodules.     These  embryonal  masses  may  undergo  a  seri'  - 
changes  resulting  in  the  production  of  simple  or  specific  inflammatory 
granulations,   such   as  infectious  nodules,   tubercles,   syphilomata. 
lepromata,  and   the  like. 

As  to  reparation  of  the  lesion,  it  may  be  complete  or  incomplete, 
viz.,  the  tissue  may  resume  its  primary  aspect  or  permanently  retain 
lesions — indelible  marks  of  the  inflammatory  process  oi  which  it  has 
been  the  seat. 


1 74  JXFECTIO  US  DISEASES. 

Iii  the  former  case  the  lesions  have  been  slight.  A  few  cells 
perished  in  the  struggle,  but  were  picked  up  and  digested  by  the 
macrophages'.  The  survivors  which,  during  the  stationary  period, 
were  in  kar.yokinesis,  rapidly  replaced  the  destroyed  elements. 

When,  however,  the  process  is  intense  or  lasts  for  a  long  period 
of  time,  complete  repair  is  impossible.  The  epithelial  elements 
undergo  too  profound  degeneration  or  perish  in  too  great  numbers. 
They  are  then  replaced  by  connective  tissue  which,  owing  to  its 
more  elementary  organization,  is  more  resistant.  A  sclerotic  tissue 
is  thus  produced  which  is  at  first  traversed  by  numerous  vessels, 
but  the  latter  are  not  endowed  with  great  vitality,  and  soon  dis- 
appear, leaving  the  cicatrix  in  a  state  of  dried  tissue. 

Serous  Exudates.  Serous  exudations  may  be  produced  in  the 
subcutaneous  cellular  tissue,  in  serous  membranes,  in  parenchymas 
like  the  lungs,  and  less  often  in  glands,  as  is  the  case  in  mumps. 
These  exudates  resemble  the  blood  serum,  but  differ  among  them- 
selves in  their  chemical  composition.  From  this  standpoint  they 
have  been  divided  into  two  classes :  One  comprises  the  inflammatory 
serosities,  with  a  specific  gravity  reaching  or  exceeding  1018.  These 
are  remarkable  for  their  richness  in  proteid  substances  and  in  fibrin, 
and  coagulate  spontaneously  in  the  air.  The  second  class  com- 
prises the  mechanical  dropsies,  which  contain  but  a  small  amount 
of  nitrogenous  substances,  and  do  not  coagulate  unless  certain 
elements,  such  as  blood  serum,  ferment  solution,  or  myosin  are 
added. 

Between  these  two  extreme  types  there  are  numerous  transitions. 
Belief  in  the  importance  of  mechanical  exudation  is  on  the  decline. 
It  is  asserted  that  even  in  cases  of  cardiac  and  Bright's  disease  serous 
exudations  are  often  ascribable  to  the  presence  of  bacteria.  Undoubt- 
edly all  edemas  should  not  be  considered  as  inflammatory  in  nature. 
Venous  stasis,  cardiac  incompetency,  renal  impermeability,  and  ner- 
vous derangements  produce  edemas  independently  of  all  inflamma- 
tory process.  These  facts  are  relatively  rare,  however,  and  most  of 
the  dropsies  of  serous  membranes  are  held  to  be  subacute  inflam- 
mations. This  view  finds  strong  support  in  the  fact  that  a  great 
many  microbes  are  capable  of  producing  edema,  as  has  experimen- 
tally been  demonstrated  with  the  bacillus  anthracis,  the  bacillus  of 
diphtheria,  and  the  streptococcus  of  erysipelas.  Nearly  all  the 
known  microbes  might  be  cited  as  capable  of  giving  rise  to  subcu- 
taneous edemas.     Among  the  most  important  may  be  mentioned 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.  [75 

the  bacterium  lymphagogon  of  Hamburger,  the  proteu<  vulgaris, 
whose  soluble  products  have  also  an  edemagenic  influence,  and  the 
staphylococcus  aureus.  The  last-named  microbe  i-  habitually  con- 
sidered as  no  more  than  a  pus  coccus.    The  author  ha*  noticed, 

however,  Mini  Hie  siihciii.-uieoii.-'  i  1  h >ci iln  1  ion  of  certain  samples  pro- 
duces considerable  edemas  proving  rapidly  fatal,  withoul  the  forma- 
tion of  pus.  This  result  is  not  surprising,  as  most,  If  nol  all,  of  the 
microbes  above  referred  to  are  ap1  to  produce  either  edema  or  sup- 
puration. In  Mie  former  case  I  he  pathogenic  agenl  is  very  virulent ; 
serous  exudation  takes  place,  1  ml  (lie  leucocytes  cannot  enter  the  field 
in  sufficient  numbers.  In  the  latter  case  the  microbe  is  less  ac 
and  migration  is  produced.  In  spile  of  appearances,  the  two  pro- 
cesses are  the  same,  differing  only  in  degree.  Anthrax,  for  instance, 
gives  rise  to  a  fatal  edema  in  the  guinea-pig  and  rabbil .  In  the  adult 
rat,  which  is  wellnigh  refractory  to  the  disease,  an  abscess  is  the 
result.  Samples  of  staphylococcus  when  attenuated  by  successive 
cultures  in  artificial  media  become  pyogenic.  The  same  is  true  of 
the  streptococcus.  According  to  the  degree  of  virulence  of  the 
sample  or  the  resistance  of  the  animal,  the  result  is  death  without 
a  local  lesion,  development  of  a  fatal  or  curable  edema,  or  production 
of  a  localized  abscess  of  little  gravity 

Our  knowledge  concerning  the  chemical  constitution  of  inflam- 
matory subcutaneous  edemas  is  very  limited.  All  we  know  is  that 
they  differ  from  blood  serum  and  lymph.  They  also  differ  from  one 
case  to  another.  They  are  not  like  the  exudates  of  the  serous  mem- 
branes. It  may,  therefore,  be  concluded  that  they  are  due  not  to 
simple  transudation,  but  to  a  sort  of  secretion,  or  at  least,  according 
to  Jaccoud's  expression,  to  a  selective  transudation. 

Pleural  exudates  have  more  particularly  attracted  the  attention 
of  chemists,  and  the  difference  between  inflammatory  and  simply 
dropsical  effusions  is  clearly  established.  The  latter  process  is  to  be 
understood  as  an  inflammation  of  subacute  or  torpid  character. 
Halliburton,  who  analyzed  three  cases  of  pleurisy  and  three  of 
hydrothorax,  gives  the  following  demonstrative  figures:  specific 
gravity  varied  from  1020  to  1023  in  the  former  instance :  from  1012 
to  1016  in  the  latter.  Proteid  substances,  in  pleurisy,  oscillated 
between  34  and  52  per  1000.  Fibrin  amounted  to  0.1  or  1 :  globulin, 
12  to  30;  and  serin,  11  to  33  per  1000.  In  hydrothorax.  proteid 
materials  did  not  exceed  13  to  25:  fibrin.  0.06  to  0.1:  and  serin.  7 
to  IS.     Globulin  varied  from  4  to  7  per  1000.     These  results  clearly 


1 76  IXFECTIO  US  DISEASES. 

show  that  inflammatory  exudates  are  denser,  richer  in  protein,  and 
especially  in  fibrin.  It  is  but  just  to  recall  that  Mehu's  researches 
already  pointed  to  these  conclusions. 

Pseudomembranes.  It  is  customary  in  Germany  to  divide  pseu- 
domembranous processes  into  two  groups,  namely,  superficial  or 
croupous,  and  diphtheritic  or  profound.  These  expressions  lead  to 
confusion,  and  must  be  abandoned.  They  correspond,  however,  to 
a  necessary  distinction.  As  a  matter  of  fact,  in  some  cases  the  false 
membrane  covers  up  a  mucous  membrane,  of  which  it  reaches  the 
most  superficial  parts  only.  In  other  instances,  the  pseudomem- 
branous exudate  results  from  a  necrosis  of  a  more  or  less  profound 
diphtheroid  gangrene.  The  former  process  is  realized  by  certain 
microbes,  notably  the  bacillus  of  diphtheria.  The  latter  process 
characterizes  the  destructive  affections  of  toxic  or  microbic  origin. 
Caustics,  such  as  silver  nitrate,  and  the  most  varied  microbes  may 
produce  lesions  of  membranous  character.  Such  is  the  case  in  ulcer- 
ating stomatitis,  which  actually  represents  a  superficial  gangrene  of 
the  mouth.  Such  is  also  the  case  in  certain  pseudomembranous 
cystites,  pyelites,  and  ententes.  The  so-called  false  membranes  are 
nothing  more  than  parts  or  shreds  of  the  altered  mucous  membrane. 

There  is,  then,  a  marked  difference  between  the  two  processes. 
The  first  is  due  to  a  general  reaction  of  the  organism;  the  second 
results  from  the  necrosing  action  of  a  pathogenic  agent.  The  former 
is  characterized  by  the  development  of  a  concrete  exudate  upon  the 
surface  of  a  mucous  membrane ;  the  latter  by  exfoliation  and  expul- 
sion of  a  pre-existing  part  which  has  been  killed. 

Leaving  aside  the  description  of  diphtheroid  gangrenes,  which  will 
be  discussed  elsewdiere,  let  us  now  consider  the  true  pseudomem- 
branous process. 

Under  the  habitual  conditions  of  life  this  process  may  be  considered 
as  always  dependent  upon  microbic  infection.  There  is  not,  how- 
ever, a  specific  diphtherogenic  microbe.  The  false  membrane  repre- 
sents a  quite  common  reaction  which  may  be  excited  by  a  number 
of  bacteria.  On  the  other  hand,  an  agent  capable  of  giving  rise  to 
the  formation  of  a  false  membrane  may  in  other  instances  produce 
an  edematous  exudation  or  a  purulent  focus.  The  difference  depends 
upon  the  virulence  of  the  microbe,  the  seat  of  the  lesion,  and  the 
condition  of  the  subject.  These  secondary  influences  intervene  in 
all  cases,  even  when  Loeffler's  bacillus  is  the  agent  concerned.  The 
diphtherogenic  action  of  this  microbe  is  manifested  only  in  parts  in 


DEFENSES  AND  IlEAOTIONS  OF  THE  ORGANISM.  177 

contact  with  air,  while  subcutaneous  inoculations  produce  only 
edema  rich  in  fibrin,  but  no  false  membrane 

It  is  :i  well-established  law  thai  the  figurate  agents  ad  only  by 
their  secretions.  This  law  is  applicable  to  the  pseudomembranouf 
processes.  It  has  for  a  long  time  been  believed  thai  false  membranes 
were  not  produced  except  under  the  influence  of  living  bacteria 
acting  upon  an  altered  mucous  membrane,  and  thai  theeffed  of  the 
toxins  was  simply  to  induce  a  vasodilatation  permitting  the  migra- 
tion of  leucocytes. 

This  conception  has  been  abandoned  in  consequence  of  experi- 
ments pursued  by  Dr.  Bayeux  and  the  author  and  the  confirmative 
researches  of  Dr.  Morax.  From  these  investigations  it  was  shown 
that  the  diphtheritic  toxin  introduced  into  the  trachea  may  be 
absorbed  by  the  respiratory  passage  and  give  rise  to  a  general  in 
cation.  This  is  what  occurs  in  animals  highly  sensitive  to  this  poison , 
such  as  the  guinea-pig.  In  rabbits,  which  are  more  resistant,  a  local 
reaction  is  often  produced,  resulting  in  the  formation  of  a  false  mem- 
brane. It  seems  that,  in  this  instance,  the  poison  exhausts  itself  in 
local  effects,  since  if  the  animal  is  sacrificed  nothing  but  mechanical 
lesions,  such  as  pulmonary  emphysema,  are  found.  Visceral  lesions, 
which  express  general  intoxication,  are  absent.  We  may,  therefore, 
extend  to  toxins  what  is  already  demonstrated  with  reference  to 
living  microbes — viz.,  that  the  local  lesion  is  the  sign  of  attenuated 
poison.  At  all  events,  it  is  produced  only  when  the  animal  is  endowed 
with  a  certain  degree  of  resistance. 

Similar  results  may  be  obtained  by  operating  upon  other  mucous 
membranes.  It  has  been  possible  to  produce  pseudomembranous 
conjunctivitis,  vulvitis,  etc.,  by  simply  depositing  the  pure  toxin  of 
diphtheria  upon  the  mucous  membrane;  but,  as  this  has  already  been 
demonstrated  with  regard  to  suppuration,  the  more  slowly  the  poison 
penetrates  the  greater  is  the  success  of  the  experiment. 

Experimental  results  explain  certain  clinical  facts  in  which  false 
membranes  were  found  to  have  extended  far  beyond  the  seat  of 
microbic  colonies.  Such  was  the  singular  case  which  the  author 
observed  with  Dr.  Gamier.1  A  false  membrane  originated  at  the 
level  of  the  superior  vocal  cords  and  epiglottis  and  extended  unin- 
terruptedly as  far  as  the  smallest  bronchial  ramifications.  .Is  may 
be  seen  in  the  figure  below,  the  false  membrane  represents  a  perfect 

1  Roger  et  Gamier.    Diphterie  traeheo-bronchique  generalise.    Presse  ni£d.,  Nov.  9, 
1898. 

12 


178 


IXFECTIO  US  DISEASES. 


mould  of  the  bronchial  tree.  Below  the  ramifications  of  the  third 
order  the  membrane  was  so  thin  that  it  was  impossible  to  extract 
more  than  fragments.  It  is  readily  conceivable  that  tracheotomy 
failed  to  relieve  the  patient,  since  the  obstruction  of  the  respiratory 

passages  was  complete. 

Fig.  1. 


Diphtheritic  false  membrane. 


The  nature  of  the  production  was  verified  by  cultures.  At  the 
time  of  admission  of  the  sufferer  a  culture  was  made  with  exudates 
taken  from  the  tonsils,  and  the  presence  of  LoefHer's  bacillus  was 
demonstrated.  At  the  necropsy  fragments  were  taken  from  the 
middle  intrapulmonary  ramifications  and  cultivated.  A  small  num- 
ber of  the  bacilli  were  found.  The  culture  tubes  inoculated  with  the 
material  from  the  last  ramifications  remained  sterile. 

The  extension  of  the  process  cannot,  therefore,  be  attributed  to 


DEFENSES  AND  REACTIONS  OF  THE  ORGANISM.  17!' 

the  propagation  of  the  bacilli,  since  their  number  dimini  bed  in  pro 
portion  to  the  distance  the  points  examined  were  from  the  lar 
and  disappeared  in  the  smallesl  branches  of  the  bronchial  tube. 

To  explain  the  production  of  pseudomembrane  .  several  the< 
have  been  advanced.  The  simplesl  idea  is  to  assume  an  exudation 
of  a  fibrinogenic  substance  which  coagulates  on  contacl  with  the  air. 
Wagner  asserts  thai  false  membranes  are  produced  by  the  celh  of 
the  tissues  which  unite  by  means  of  prolongations.  Ii  Ls  qow  gen- 
erally admitted  that  an  exudate  is  constituted,  on  the  one  hand,  of 
fibrinogenic  substance  and,  on  the  other,  of  altered  cells.  The  fibrino- 
genic  substance  escapes  from  the  vessels  and  finds  the  besl  condi- 
tions for  coagulating— it  is  in  contacl  with  the  air,  it  meete  with 
dead  leucocytes  which  here,  as  everywhere,  play  a  greal  pari  in 
coagulation;  it  is  spread  out  upon  a  mucous  membrane  the  cells  of 
which  are  diseased.  From  the  time  of  Cohnheim  and  Weigerl  it  has 
been  known  that  epithelia  as  well  as  endothelia  do  not  oppose  the 
coagulating  of  exudations  except  when  they  are  intact.  At  the  same 
time  a  certain  role  is  to  be  attributed  to  the  cells  of  tissues  which 
become  fibrinified  according  to  the  process  described  by  Weigerl 
under  the  name  coagulation  necrosis. 

Thus,  made  up  at  the  expense  of  the  fibrin  of  the  blood  and  of 
the  cells,  false  membranes  appear  under  variable  aspects.  They  may 
be  found  in  serous  exudates  where  they  float  in  the  fluid.  In  other 
cases  they  are  more  abundant  and  line  the  two  surfaces  of  the  serous 
membrane,  and  may  cause  them  to  adhere.  Lastly,  they  are  not 
infrequently  seated  upon  the  surface  of  a  mucous  membrane,  adher- 
ing to  it  more  or  less  intimately. 

Should  one  of  these  pseudomembranes  be  stripped  off.  an  ulcerate*  1 . 
slightly  bleeding  surface  is  exposed,  which  clearly  proves  that  we  are 
dealing  not  with  a  simple  deposit,  but  a  more  profound  lesion. 

The  detached  false  membrane  is  sufficiently  resistant.  It  does 
not  disintegrate  when  agitated  in  water,  thus  being  distinguished 
from  pultaceous  layers  or  mucous  accretions.  It  is  dissolved  by  lime- 
water  and  by  sodium  hypochlorite :  its  richness  in  fibrin  explains  why 
it  decomposes  oxygenated  water. 

Under  the  microscope  a  false  membrane  is  found  to  be  composed 
of  anastomosed  fibrinous  threads,  sending  out  prolongations  which 
attach  themselves  to  the  subendothelial  tissues  by  a  series  of  arcades. 
This  explains  why  the  production  is  adherent.  The  fibrin  appears 
in  the  form  of  lamellae,  compact  masses,  or  spiral  threads.     In  the 


180  INFECTIOUS  DISEASES. 

midst  of  the  fibrin  can  be  seen  mucin,  fat,  altered  cells,  and  in  most 
cases,  numerous  microbes. 

The  false  membrane  may  grow  by  the  addition  of  new  layers  of 
fibrin  and  be  reproduced  when  it  is  stripped  off.  The  considerable 
amount  of  fibrin  which  may  thus  be  eliminated  is  not  to  be  wondered 
at.  Dr.  Dastre  has  demonstrated  how  rapidly  this  substance  is  pro- 
duced in  the  organism.  If  the  greater  part  of  the  blood  of  a  dog 
be  defibrinated  and  again  introduced  into  the  vessels,  it  will  soon  be 
found  that  the  blood  has  become  as  rich  in  fibrin  as  normal. 

When  a  false  membrane  occupies  the  surface  of  a  mucous  mem- 
brane, that  of  the  throat  for  instance,  a  time  will  come  in  fortunate 
cases  when  the  secretions  of  the  subjacent  glands  will  detach  the 
pseudomembrane  and  cause  its  exfoliation.  The  remaining  adherent 
particles  will  be  removed  by  the  phagocytes.  This  process  may  be 
assisted  by  means  of  pilocarpine  which,  by  stimulating  glandular 
secretion,  hastens  exfoliation  of  the  pathological  membranes.  In 
some  instances  the  latter  disappear  in  consequence  of  a  histochemical 
transformation.     They  undergo  a  granular  or  hyaline  degeneration. 

In  other  cases  in  tissues,  and  particularly  in  serous  membranes, 
the  false  membrane,  instead  of  disappearing,  becomes  organized.  The 
fixed  and  the  wandering  cells  proliferate,  and  the  tissue  becomes 
vascularized.  In  this  manner  are  formed  adhesions  which  may 
subsequently  be  absorbed,  or  undergo  sclerotic  transformation,  or 
become  infiltrated  with  calcareous  salts. 

The  production  of  false  membrane  must  be  considered  as  a  phe- 
nomenon of  defensive  reaction.  It  is  a  barrier  opposed  to  the  pene- 
tration of  microbes  and  toxins.  In  some  cases  it  is  a  reinforcement 
of  tissues,  preventing  their  destruction  under  the  influence  of  patho- 
logical causes.  This  is  equally  true  as  regards  the  false  membranes 
developing  upon  serous  membranes. 

In  this  mode  of  defensive  reaction,  as  in  other  instances,  excess  is 
often  possible.  The  diphtheritic  false  membrane  may,  by  reason  of 
its  location,  cause  grave  and  fatal  disturbances  of  a  mechanical 
order.  The  adhesions  of  serous  membranes  embarrass  the  move- 
ments of  subjacent  viscera,  give  rise  to  deformities,  compress  impor- 
tant organs  or  excretory  passages,  and  thus  bring  in  their  train  a 
whole  series  of  morbid  manifestations. 

Although  the  process  is  somewhat  different,  the  production  of 
exudates  rich  in  fibrin,  as  well  as  those  produced  by  the  pneumo- 
coccus,  may  be  compared  to  false  membranes.     The    expression 


DEFENSES  AND  REACTIONS  OF  THE  ORG  iNISM.         |  >sl 

"croupous  pneumonia,"  a1  times  applied  to  the  pneumococcic  inflam- 
mation, suggests  this  analogy.  We  find  \\\<-  same  pathogenesi 
the  pneumococcic  exudates  as  for  diphtheritic  productions.  The 
investigations  of  C;iniot  establish  thai  they  depend  upon  micTobic 
toxins.  Their  signification  is  identical  in  both  cases.  They  are 
lesions  intended  to  protect  Ihc  organism  againsl  the  penetration  of 
microbes  and  of  toxins.  <  )n  taking  into  accounl  the  oature  of  these 
two  sorts  of  exudates,  we  reach  the  conclusion,  which  ie  equally  thai 
of  Gilbert  and  Founder,  that  fibrin  piny-  a  defensive  rdle  of  consid- 
erable importance. 


CHAPTER   VII. 

SUPPURATION. 

Division  of  Pyogenic  Microbes  into  Five  Groups:  The  Habitual,  the  Specific,  the 
Accidental,  the  Vegetable,  and  the  Protozoic  Pyogenics.  Relative  Frequency 
of  Various  Pyogenic  Agents.  Distribution  of  Pyogenic  Microbes  in  and  Outside 
the  Organism.  Causes  Favoring  Suppuration:  Importance  of  Number  and 
Virulence  of  Microbes;  of  the  Mode  of  Entrance;  of  Previous  Lesions.  Gener- 
alization of  Suppurating  Processes.  Amicrobic  Suppurations.  Role  of  Soluble 
Substances  in  the  Production  of  Pus.  Physical  and  Chemical  Characters  of  Pus. 
Mode  of  Development  and  Evolution  of  Suppurations.  Hot  and  Cold  Abscesses. 
Suppuration  in  the  Various  Parts  of  the  Organism. 

From  a  histological  standpoint,  suppuration  is  essentially  char- 
acterized by  the  formation  of  an  exudate  containing  very  large 
numbers  of  round  cells,  more  or  less  similar  to  leucocytes.  These 
cells,  therefore,  became  the  first  subject  of  research.  Virchow 
believed  they  were  derived  from  the  fixed  cells  of  the  inflamed  tissue. 
Cohnheim  contended  that  pus  corpuscles  were  nothing  else  than  leuco- 
cytes which  had  left  the  vessels  by  migration.  Each  of  these  con- 
ceptions, as  we  shall  see  later,  contained  some  part  of  the  truth, 
but  they  did  not  solve  the  problem.  It  was  necessary  to  discover 
the  influences  which  caused  the  round  cells  to  accumulate  in  an  organ 
or  tissue  and  the  conditions  under  which  inflammation  terminated 
in  suppuration. 

During  the  epoch  of  Virchow  it  was  admitted  that  any  cause  of 
irritation  could  induce  suppurative  inflammation.  Later,  it  was 
asserted,  on  the  contrary,  that  the  various  physical,  mechanical, 
and  chemical  excitants  are  incapable  of  producing  pus  unless  the 
foreign  body  introduced  has  special  specific  properties,  viz.,  unless 
it  serves  as  the  vehicle  of  pyogenic  microbes.  Caspard,  as  early  as 
1822,  and  after  him,  Gunther,  d'Arcet,  Castelneau,  and,  above  all, 
Sedillot,  showed  by  experiments  that,  when  injected  beneath  the 
skin  or  into  the  serous  membranes,  pus  can  produce  suppuration, 
but  did  not  demonstrate  the  specific  nature  of  the  process. 

In  1872  Chauveau  pointed  out  that  the  phlogogenic  power  of  pus 
depends  not  upon  the  serum,  but  upon  the  solid  parts ;  that  the  pus 
corpuscles  possess  a  special  property,  while  the  mineral  substances 
and  the  cells  derived  from  the  lymphatic  glands  are  not  capable  of 


SUPPURATION.  183 

giving  rise;  to  suppuration.     It  was  thus  established  thai  all  foreign 
bodies  are  not  pyogenic,     'the  nature  and  cau  ation  of  the  prin 
focus  remained  to  be  determined. 
Lister  admitted  the  role  of  germs  without,  however,  believing  thai 

their  intervention  is  indispensable,  lie  supposed  thai  suppuration 
may  be  referable  to  other  causes,  for  instance,  the  acl  ion  of  chemical 
agents  or  the  influence  of  some  nervous  disturbance.  From  thai 
epoch  onward  attention  was  called  to  the  role  of  microbic  agents. 
In  1872,  Klebs  described  a  microsporon  seplicum,  capable  of  pro- 
ducing pus.  I"  I<s7.r)  Bergeron  noticed  the  presence  of  vibriorii  in 
the  pus  of  acute  abscesses.  Kocher,  studying  a  greal  aumber  of 
abscesses,  constantly  found  bacteria,  and  was  thus  led  to  the  con- 
clusion that  there  is  probably  no  suppuration  without  microbes. 
This  was  also  the  opinion  of  Cheyne,  Koch,  and  Cornil,  and  it  gen- 
erally seems  to  be  true  in  practise. 

Under  certain  conditions  almost  all  microbes  are  capable  of  exert- 
ing pyogenic  action.  In  order  to  facilitate  description,  howevei 
may  artificially  divide  them  into  four  groups:  First,  the  habitual 
agents  of  suppuration,  the  pyogenics,  properly  so-called.  Not  that 
they  are  found  only  in  purulent  foci — since  the  staphylococcus  has 
been  met  with  in  serous  exudates,  in  pleurisies,  in  rheumatism,  and 
the  same  is  true  of  the  streptococcus — but  because  we  consider  that 
their  most  characteristic  property  is  the  production  of  pus  in  the 
organism.  Secondly,  unlike  the  common  pyogenic  microbes  which 
are  abundantly  distributed  in  nature,  and  often  live  as  epiphytes  or 
saprophytes,  there  are  specific  pyogenics,  always  pathogenic  and 
always  creating  suppurative  lesions.  This  group  includes  five  spe- 
cies: the  diplococcus  of  cerebrospinal  meningitis,  the  micrococcus  of 
gonorrhea,  the  bacillus  of  soft  chancre,  the  bacillus  of  glanders,  and 
the  bacillus  of  bubonic  plague.  The  thud  group  comprises  microbes 
which  are  quite  different  from  the  preceding — specific  agents  which 
habitually  produce  well-defined  diseases,  such,  for  instance,  as  the 
microbes  of  typhoid  fever  or  of  influenza.  These  become  pyogenic 
only  under  special  conditions,  to  be  referred  to  later.  Finally,  in  a 
fourth  division  it  is  convenient  to  group  those  pyogenic  agents  which 
do  not  belong  to  the  class  of  bacteria. 

The  following  table,  although  incomplete,  comprises  the  principal 
parasites  capable  of  inducing  suppuration: 


184  INFECTIOUS  DISEASES. 


1.  Pyogenic  Bacteria. 
Staphylococci. 

Staphylococcus  pyogenes  aureus  (Rosenbach). 

Staphylococcus  pyogenes  citreus  (Passet). 

Staphylococcus  pyogenes  albus  (Rosenbach') . 

var. :  Staphylococcus  salivarius  pyogenes  (Biondi). 
Staphylococcus  of  Alrnquist. 

Staphylococcus  pyosepticus  (Hericourt  and  Richet). 
Staphylococcus  epidermidis  albus  (Welch). 
Microbe  of  the  Biskra  button  (Duclaux). 
Streptococci. 

Streptococcus  pyogenes  (Rosenbach). 
Streptococcus  erysipelatis  (Fehleisen). 
Streptococcus  articulorum  (Loeffler). 
Streptococcus  pyogenes  malignus  (Fliigge). 
Streptococcus  septicus  (Nicolaier  and  Guarnieri). 
Streptococcus  septopyemicus  (Eberth  and  Wolff). 
Streptococcus  conglomeratus  (Kurth). 
Streptococcus  ramosus  (Roger  and  Weil). 
Streptococcus  of  acute  Bright's  disease  (Manneberg). 
Streptococcus  equi  (Schutz). 
Streptococcus  ruber  (Lundstrom). 

Streptococcus  of  contagious  mammitis  of  the  cow  (Nocard  and  Mollereau). 
Streptococcus  septicus  liquefaciens  (Babes). 

Streptococcus  pneumoniae  (pneumonococcus  of  Talamon-Fraenkel) . 
Micrococcus  pyogenes  tenuis  (Rosenbach). 
Micrococcus  pneumoniae  (Ortner). 
Microbe  of  pneumonia  of  the  horse  (Schutz). 
Other  micrococci. 

Micrococcus  tetragenus  (Koch,  Gaffky). 
Micrococcus  gingivae  pyogenes  (Miller). 
Micrococcus  endocarditis  rugatus  (Weichselbaum). 
Micrococcus  subflavus  (Fliigge). 
Micrococcus  pyogenes  fetidus  (Veillon). 
Staphylococcus  parvulus  (Veillon  and  Zuber). 
Diplococcus  reniformis  (Cottet). 

Micrococcus  of  gangrenous  mammitis  of  the  lamb  (Nocard). 
Micrococcus  of  necrosis  of  the  mouse  (Koch). 
Micrococcus  of  pyemia  of  rabbits  (Koch). 
Micrococcus  of  progressive  suppuration  of  rabbits  (Koch). 
Bacilli. 

Bacillus  coli  (Escherich). 

B.  lactis  aerogenes  (Escherich). 

B.  pyogenes  fetidus  (Passet). 

B.  burci. 

B.  endocarditis  griseus  (Weichselbaum)., 

B.  enteritidis  (Gaertner). 

Pyobacillus  Fischeri. 
Pneumobacillus  (Friedlaender) . 

B.  meningitidis  purulent®  (Neumann  and  Schaeffer). 
B.  sycosis  (Tommasoli). 
Bacillus  of  noma  (Schimmelbusch). 
B.  pyogenes  soli  (Bolton). 
B.  dentatis  viridans  (Miller). 
Proteus  Zenkeri. 

Bacillus  fetidus  liquefaciens  (Lenz). 
B.  nephritidis  (Letzerich). 
B.  pulpaj  pyogenes  (Miller). 
B.  gingivae  pyogenes  (Miller). 
B.  capsulatus  (Chiari). 
Proteus  vulgaris  (Hauser). 
Proteus  mirabilis  (Hauser). 
Proteus  pleomorphus  (Karlinski). 
Bacillus  saprogenes  II.  (Rosenbach). 
Bacillus  saprogenes  III.  (Rosenbach). 
B.  pyogenes  gazeigenes  (Levy,  Fraenkel). 
B.  perfringens  (Veillon  and  Zuber). 
B.  ramosus  (Veillon  and  Zuber). 
B.  serpens  (Veillon  and  Zuber). 
Bacillus  fragilis  (Veillon  and  Zuber). 


SUPPURATION.  I  -.", 

B,  fusiformia  ( Veillon  and  Zuber). 

B.  furcosus  (Veillon  and  Zuber). 

Btreptobacillus  pyogenes  floccosus  (P,  Courmont  and  Cadi 

2.    Sit. en  i«     PyoOE     [I     BAC1  EM  *. 

I  (iplocncctlS    nil  t'lK'.cl  1 1 1 1.T  1  i       1 1  n  i   i  m  "  1 1  1 1 1  i  I, 
(  lOMOOOCCllH. 

Bacillus  of  soft  ohanore. 

I  tacillus  of  glanders. 

I  tacillus  of  t  lie  bubonic  plague, 

:{.  A.CCIDBNTA1  Pyoqj    to  Bacteria, 
Bi  anthracis. 
I».  of  gaseous  gangrene. 
B.  of  symptomatic  anthrax. 
I '..  of  hemorrhagic  sei >\  Lcsemis . 
B.  of  purulent  rhinitis  of  the  rabbil , 
I'),  of  tuberculosis. 
B.  of  pseudotuberculosis. 
B.  <>f  influenza . 
B.  of  typhoid  fever. 

4.  Pyogenic  Plants, 
Streptothrix  or  oospora  astcroides. 
Strcptothrix  or  oospora  Hofmani. 
Streptothrix  or  oospora  Gruberi. 
Actinomyces  (oospora  bovis). 
Oospora  madurse. 
Aspergillus  fumigatus. 
Penicillium. 
Mucor  (corvmbifer  ?). 
Botrytis  (?) 
Various  yeasts: 

Cryptococcus  farcinosus. 

Oidium  albicans. 

Trichophyton  mentagrophytes. 

Trichophyton  felineum. 

5.  Pyogenic  Protozoa. 
Ameba  coh. 
Protozoon  of  variola. 
Protozoon  of  varicella. 
Protozoon  of  vaccinia. 

1.  Pyogenic  Bacteria. 
Staphylococcus.  The  type  of  the  habitually  pyogenic  microbe  is 
represented  by  the  staphylococcus  pyogenes  aureus.  It  was  discov- 
ered by  Ogston  in  1881,  and  fully  described,  in  1884,  by  Rosebach. 
It  is  a  facultative  anaerobe  developing  readily  in  the  majority  of 
media  employed  in  bacteriology.  Examined  under  the  microscope, 
the  staphylococcus  aureus,  as  well  as  albus  and  citreus.  appears  in 
the  form  of  small,  rounded  elements,  measuring  from  0.7 ft  to  1.5ft. 
The  smallest  elements  are  seen  in  old  cultures,  the  largest  in  cultures 
kept  at  109.4  F.  (43  C).  In  pus  the  cocci  are  disseminated  in  the 
form  of  monococci  or  diplococci.  In  cultures  they  are  generally 
united  in  masses,  presenting  at  times  the  aspect  of  a  bunch  of  gr: 
Hence,  the  name  given  to  this  species.  More  frequently,  however, 
these  cocci  are  grouped  in  such  a  manner  as  to  form  large  anasto- 
mosed bands  circumscribing  empty  spaces. 


186  INFECTIOUS  DISEASES. 

The  chromogenic  function  which  characterizes  the  staphylococcus 
aureus  has  no  specific  value.  This  microbe  ceases  to  secrete  its 
pigment  when  cultivated  in  the  absence  of  air,  or  when  small  amounts 
of  antiseptic  substances,  such  as  antipyrin,  are  added  to  the  medium, 
or  when  the  culture  is  exposed  to  strong  sunlight.  The  different 
staphylococci  are,  therefore,  considered  rather  varieties  of  one  spe- 
cies. Owing  to  its  greater  power  of  multiplication  and  more  ener- 
getic pathogenic  potency,  the  staphylococcus  aureus  is  the  leading 
species.  Next  comes  the  staphylococcus  citreus,  followed  by  the 
albus,  whose  cultures  are  not  pigmented.  Starting  with  the  aureus, 
it  is  easy  to  obtain  the  colorless  variety.  The  reverse  is  less  fre- 
quently realized.  Dr.  Netter  has,  however,  seen  a  staphylococcus 
albus  converted  into  aureus. 

Streptococcus.  A  great  number  of  streptococci  have  been  de- 
scribed. The  present  tendency,  at  least  in  France,  is  to  regard  them 
as  varieties  of  a  single  species.  In  fact,  the  different  characters 
described  by  authorities  are  rather  uncertain  and  may  disappear  in 
successive  cultures.  Researches  in  serotherapy,  however,  lead  us 
again  to  subdivide  the  group,  since  the  serum  of  an  animal  immunized 
against  one  variety  does  not  combat  infection  by  all  streptococci. 
The  presence  of  micrococci  in  the  form  of  chains  had  been  noticed 
by  Coze  and  Feltz  in  various  organic  fluids.  Pasteur  and  Doleris 
subsequently  discovered  similar  elements  in  puerperal  infection. 
Their  presence  in  pus  was  pointed  out  by  Ogston,  then  by  Rosenbach 
and  Posset,  who  made  a  complete  study  and  endeavored  to  differen- 
tiate it  from  the  streptococcus  of  erysipelas,  discovered  by  Fehleisen. 
The  streptococcus  develops  quite  readily  in  various  media  employed 
for  cultures.  In  agar-agar  it  generally  vegetates  in  the  form  of  very 
small,  rounded,  somewhat  hemispheroid,  semitransparent,  or  opaque 
white  colonies.  These  colonies  are  generally  isolated,  except  in  very 
active  cultures  in  which  they  may  become  confluent. 

The  streptococcus  is  a  facultative  anaerobe.  Some  specimens 
develop  more  luxuriantly  without  than  with  air  and,  withal,  better 
preserve  their  virulence  and  secrete  more  active  toxins.  Under  the 
microscope  the  streptococcus  appears  in  the  form  of  chains  made  up 
of  four  to  forty  elements.  The  chains,  which  are  rather  short  in 
solid  media,  are  much  longer  in  liquid  media,  and  particularly  in 
serum.  Authorities  have  described  different  species  of  this  coccus 
according  to  cultural  characters,  morphology,  and  pathogenic  action. 

Behring  first  divides  streptococci  into  two  groups  according  as  the 


SUPPURATION.  187 

chains  are  long  or  short.     The  shorl  one,  streptococcus   brevis,  i-  & 
saprophyte]  the  long,  streptococcus  longus,  i    divided  ■<    fol 

1 .  S.  rendering  bouillon  I  urbid 

S.  of  erysipelas. 
S.  pyogenes. 
S.  of  anginas. 

2.  S.  M«>(,  rendering  bouillon  turbid, 

«.   Producing  a  mucous  depo  ii , 
S.  of  phlegmon. 
S.  of  bronchopneumonia. 
S.  of  puerperal  Lnfed  ion. 

b.  Producing  flocculi. 

S.  of  scarlet  fever  (S.  conqlomeratu 
S.  of  gravr  pycmi.M. 

c.  Producing  large  masses  adhercnl   in  the  walls  "I"  the  tube. 

S.  of  equine  pneumonia . 

It  would  be  more  rational  to  base  a  classification  upon  results 
obtained  by  inoculations  into  animals  than  upon  modifications 
observed  in  the  form  of  the  elements  and  appearance  of  the  cultures. 
Under  these  conditions  four  varieties  of  streptococci  should  be 
admitted:  saprophytic,  septicemic,  pyogenic,  and  erysipelatogenic. 
Experimental  and  clinical  studies  demonstrate,  however,  thai  the 
pathogenic  varieties  easil}r  fall  into  the  rank  of  saprophytes.  Recip- 
rocally, most  of  the  non-virulent  cultures  are  capable  of  exaltation- 
The  microbe  first  becomes  capable  of  producing  pus,  then  of  giving 
rise  to  erysipelas,  and,  finally,  to  septicemia.  This  result  having 
been  verified  by  many  authorities,  has  led  to  the  admission  of  two 
principal  species,  pyogenic  and  erysipelatogenic,  in  which  all  the 
other  varieties  have  been  included. 

Pneumococcus.  The  belief  that  the  pneumococcus  is  related  to 
the  streptococcus  has  gradually  gained  ground.  Some  bacteriolo- 
gists even  co'nsider  it  to  be  a  variety  of  true  streptococci.  In  support 
of  this  view,  it  ma}r  be  recalled  that  there  are  certain  microbic  forms 
constituting  transitions  between  the  extreme  types.  Until  the  con- 
trary is  proven,  however,  it  is  more  rational  to  consider  the  pneu- 
mococcus of  Talamon-Fraenkel  as  a  different  species.  Its  pyogenic 
role  needs  no  further  demonstration.  There  is  already  abundant 
observation  showing  that  this  microbe  is  capable  of  producing  sup- 
puration in  the  lungs  or  elsewhere.  Contrary  to  an  opinion  formerly 
advanced,  it  is  now  known  that  postpneumonic  abscesses  may  be 
created  under  its  influence  without  the  co-operation  of  any  other 
microbe. 

There  are  other  pyogenic  micrococci,  among  which  the  microc<: 


188  rJV FEC TIO  US  DISEA  SES. 

tetragenus  occupies  an  important  place.      Chauffard  and  Ramond 

believe  that  it  can  produce  septicemias,  and  I  have  frequently  found 
it  in  cases  of  sore  throat,  in  which,  however,  it  was  associated  with 
various  other  microbes  (p.  44).  Being  almost  constantly  present 
in  the  buccopharyngeal  cavities,  the  tetragenus  is  found  in  the 
abscesses  developing  in  this  region.  It  is  met  with  particularly  in 
dental  abscesses,  cervical  adenites,  otites,  mastoidites,  suppurations 
of  nasal  origin,  pulmonary  abscesses,  purulent  bronchitis,  and  in  the 
pus  of  tuberculous  cavities.  Karlinski  has  found  it  in  tubercles,  and 
Babes  in  pyohemia,  I  have  found  it  in  the  thick,  yelloAv  discharge 
of  an  otitis  developed  in  a  child  convalescent  from  scarlatina. 

The  other  pyogenic  micrococci  are  far  less  important. 

Pyogenic  Bacilli.  The  bacillus  coli  unquestionably  heads  the  list 
of  pyogenic  bacilli.  Abundantly  distributed  throughout  the  alimen- 
tary canal,  it  is  naturally  met  with  in  suppurations  occurring  in  and 
around  the  digestive  tract  and  aroimd  the  genito-urinary  apparatus. 
It  may,  however,  easily  migrate  from  these  primary  foci  and  induce 
secondaiy  suppurations  in  distant  parts,  or  even  a  general  infection 
— a  pyemia. 

The  morphology  of  this  bacillus  is  very  variable.  It  most  fre- 
quently occurs  in  the  form  of  small  rods,  with  rounded  ends,  measur- 
ing from  2/j.  to  4/*  in  length  and  0.7//  to  Iju  in  breadth.  It  some- 
times appears  in  the  form  of  oval  elements,  which  at  first  may  be 
mistaken  for  micrococci.  At  times  it  is  isolated,  at  others  grouped 
in  pairs,  or  it  becomes  elongated  to  such  an  extent  as  to  form  fila- 
ments which  are  often  constricted  at  several  points  in  its  length. 
Finally,  if  we  add  that  there  are  motile  and  non-motile  forms ;  that 
the  appearance  of  cultures  in  agar-gar  and  gelatin  and  upon  potato 
is  not  uniform;  that  the  so-called  specific  characters  are  inconstant 
and  variable;  that  some  samples  ferment  sugar  and  others  do  not, 
and  that  certain  cultures  produce  indol,  others  furnish  none,  it  will 
be  understood  how  delicate  interpretation  becomes.  With  the  typical 
colon  bacillus  Gilbert  has  grouped  and  described  the  paracolon  bacilli 
which  present  pronounced  deviations  from  the  classical  type.  It  is 
certain  that  the  group  of  colon  bacilli  includes  species  which  will 
some  day  be  differentiated.  The  reason  division  is  not  more  ad- 
vanced is  that  none  of  the  properties  seem  to  be  absolutely  constant. 
It  is  convenient,  therefore,  to  include  the  various  forms  under  the 
same  denomination,  as  is  done  with  the  streptococci. 

Among  the  bacilli  at  present  believed  to  be  related  to  B.  coli  there 


SUPPURATION.  189 

is  the  11.  lactis  aerogenes,  discovered  by  Eschcrich  in  the  stoolf  ol 
infants.  Close  to  this  bacillus  standi  the  pneumobacillu  of  Fried- 
laender.  Between  these  two  organisms  pronounced  analogies  may 
readily  be  observed.  The  presence  of  a  capsule  i  a  character  too 
contingent  to  be  of  sped  lie  value.  The  I  wo  microbe*  cannot  b< 
better  differentiated  by  their  action  upon  animals,  since  we  have 
shown  that,  contrary  to  classical  opinion,  the  bacillus  of  Friedlaender 
is  pathogenic  for  the  rabbit.  Hence,  the  attempl  of  eminenl  scien- 
tists, such  as  Denys,  to  regard  the  two  bacilli  as  identical.  The 
question  is  and  will  long  remain  a  delicate  one.  Therefore,  withoul 
pretending  to  offer  a  definite  solution,  I  have  1  hough  1  if  sufficienl  to 
point  out  the  analogies  of  I  he  two  microbes  and  to  recall  the  pyogenic 
power  of  the  pneumobacillus.  Akin  to  this  microbe  is  the  one 
described  by  Passet  under  the  name  pneumobacillus  dhnlicher,  which 
was  found  by  the  author  in  an  abscess  and  which  produces  suppura- 
tion in  animals,  and,  finally,  the  encapsulated  bacillus  which  Chiari 
detected  in  suppurative  nephritis,  prostatites,  otites,  and  menin- 
gites. 

Anaerobic  Pyogenic  Bacteria.  While  common  suppurations  are 
generally  clue  to  aerobic  microbes,  the  anaerobic  seem  to  piny  a 
considerable  role  in  the  development  of  gangrenous  or  putrid  ab- 
scesses and  phlegmons.  Levy  isolated  from  a  gaseous  abscess  a  small 
anaerobic  abscess  which  he  failed  to  cultivate  beyond  the  first  gen- 
eration. This  is  probably  the  same  microbe  which  Fraenkel  again 
met  with  in  three  cases.  Inoculation  of  cultures  gave  rise  to  gaseous 
gangrene  in  animals — a  new  illustration  of  the  relationship  existing 
between  suppuration  and  gangrene. 

Examining  sixty  samples  of  pus,  Lubinski  found  anaerobic  bacilli 
twice.  Similar  findings  have  been  made  by  various  authorities  who 
are  at  present  inclined  to  admit  that  anaerobics  play  the  principal 
part  in  the  development  of  suppurations  in  the  urinary  apparatus 
(Albarran,  Cottet),  genital  apparatus,  at  least  in  women  (Veillon. 
Zuber,  Dujon,  Halle),  and  certain  portions  of  the  alimentary  canal 
(Veillon  and  Zuber). 

One  of  the  most  important  bacilli  isolated  by  experimenters  seems 
to  be  the  B.  ramosus.  which  is  supposed  to  be  the  chief  agent  in 
appendicitis.  In  conjunction  with  it  we  must  mention  the  B.  per- 
fringens,  analogous  to  or  identical  with  the  anaerobic  bacillus  of  Levy 
and  Fraenkel;  the  B.  fusiformis.  the  B.  serpens,  the  B.  jragilis.  the 
B.  furcosus.  and  the  staphylococcus  parvulus.     A  detailed  description 


1 90  INFECTIO  US  DISEASES. 

of  all  these  species  will  be  found  in  the  interesting  memoire  of  Veillon 
and  Zuber.1  It  will  suffice  to  note  here  that  these  various  agents, 
when  inoculated  into  animals,  give  rise  to  abscesses  or  phlegmons. 
Some  of  them,  only  slightly  noxious  when  alone,  become  highly  viru- 
lent when  associated  with  other  species.  Such  is  the  case  with  B. 
serpens  when  it  is  inoculated  along  with  the  B.  ramosus. 

Among  the  anaerobics  which  intervene  in  suppurations  of  the 
urinary  passages  the  most  interesting  is  the  diplococcus  renijormis 
(Cottet),  which  produces  urinary  and  periurinary  abscesses,  pyone- 
phroses,  and  cystites.  By  its  morphological  characters  it  resembles 
the  gonococcus,  with  which  it  has  probably  often  been  confounded. 

2.  Specific  Pyogenic  Bacteria. 

Five  microbes  at  present  make  up  this  group.  They  differ  from 
the  agents  which  we  have  thus  far  studied  in  that  they  always  give 
rise  to  suppuration  and  that  this  suppurative  process  has  special 
characters  previously  established  by  clinical  observation.  Bacte- 
riology has  done  no  more  than  confirm  the  data  of  clinical  experience. 

The  microbes  of  cerebrospinal  meningitis,  gonorrhea,  soft  chancre, 
glanders,  and  bubonic  plague,  although  pyogenics,  deserve  to  be 
grouped  in  a  special  class.  The  gonococcus  resembles  common  pyo- 
genics in  some  respects.  Like  the  latter,  it  is  said  to  be  capable  of 
vegetating  as  an  epiphyte  upon  healthy  mucous  membranes.  From 
this  point  of  view,  the  bacillus  of  soft  chancre  or  bacillus  of  Ducrey 
occupies  a  higher  rank.  Finally,  the  bacillus  of  glanders  assumes 
a  position  of  transition  between  the  pyogenics  and  the  specific  agents, 
such  as  the  tubercle  bacillus. 

3.  Bacteria  Accidentally  Pyogenic. 

Highly  differentiated  microbes,  capable  of  producing  well-defined 
diseases,  give  rise  to  no  more  than  abscesses  when  they  are  atten- 
uated or  inoculated  into  animals  not  very  sensitive  by  nature  or 
rendered  artificially  more  or  less  immune.  Such,  for  instance,  is  the 
case  with  anthrax,  the  inoculation  of  which  into  old  rats  causes  only 
an  abscess.  The  same  is  true  with  regard  to  the  virus  of  gaseous 
gangrene  or  symptomatic  anthrax  when  inoculated  into  animals 
which  have  been  subjected  to  incomplete  vaccinations.  An  analo- 
gous example  is  furnished  by  the  microbe  of  chicken  cholera,  which 

1  Veillon  and  Zuber.  Recherches  sur  quelques  microbes  strictement  anaerobies.  Arch. 
de  med.  exper.,  1898,  p.  517. 


SUPPURATION.  19] 

causes  a  speedily  fatal  septicemia  in  chicken  and  rabbits,  bul  pro- 
duces only  a  more  or  less  extensive  uppural  ion  in  guini  while 
in  man  it  gives  rise  to  qo  inure  than  a  circumscribed  ab  c<  .  a  the 
author  was  able  to  observe  in  consequence  of  an  accidental  inocu- 
lation. 

We  need  hardly  recall  I  ba1  I  he  bacillus  of  I  uberculosis  may  become 
pyogenic.  Everyone  is  acquainted  with  the  frequency  of  cold, 
cutaneous,  osseous,  or  articular  suppurations  in  which  no  other  para- 
site is  found.  Whal  is  accomplished  by  Koch's  bacillus  U  equally 
realized  by  the  bacillus  of  pseudotuberculosis.  Either  tubercles 
or  pus  is  obtained,  according  to  the  anima]  experimented  upon  or 
the  mode  of  introduction. 

Of  all  accidental  pyogenic  microbes  the  mosl  interesting  i-  that 
of  typhoid  fever.  Numerous  experimental  researches  have  demon- 
strated (hat  this  microbe  can  produce  abscesses  in  animals.  The 
pure  bacillus  of  Eberth  lias  been  met  with  in  a  certain  number  of 
suppurative  lesions  consecutive  to  typhoid  fever.  Dehu,  in  his 
thesis  (1893),  collected  forty  observations.  According  to  Chante- 
messe  and  Widal,  these  suppurations  are  most  frequently  observed 
in  the  bones;  then,  in  order  of  decreasing  frequency,  in  the  meninges, 
pleura,  peritoneum,  and  S}rnovial  membrane.  The  thyroid  and  the 
testicles  are  the  two  glands  in  which  it  is  not  infrequently  localized. 
The  spleen  is  the  only  visciis  in  which  such  process  lias  been  noted. 
The  course  is  at  times  acute,  but  more  frequently  its  evolution  is 
slow.  In  the  latter  instance  we  have  to  deal  with  cold  suppurations. 
Such  is  the  case  particularly  in  osteomyelitis  with  successive  exacer- 
bations, which  are  prolonged  for  years,  and  the  same  is  true  in  tuber- 
culous osteitis.  These  facts  should  be  remembered,  as  they  are  not 
extremely  rare.  Their  complete  history  will  be  found  in  the  work 
of  Chantemesse  and  Widal.1 

4.  Vegetable  Pyogenic  Parasites. 

Several  species  of  streptothrix  or  oospora  are  capable  of  producing 
suppuration  in  man  and  animals.  The  most  important  is  incontest- 
able- the  oospora  astcroides,  discovered  by  Eppinger  in  a  cas 
meningitis  and  again  found  under  analogous  conditions  by  Almquist. 
The  same  parasite  has  been  seen  by  Ferre  and  Faguet  in  a  cerebral 
abscess;  by  Sabrazes  and  Riviere  in  the  sputa  of  a  patient,  in  the 

1  Chantemesse  and  Widal.    Des  suppurations  froides  consecutive  a  la  fievre  typhoide. 
Soeicte  medicate  des  hopitaux.  November  24.  1S93. 


192  IXFECTIO  US  DISEASES. 

pus  of  subcutaneous  abscesses,  and  in  abscesses  of  the  brain  and 
kidney.  We  will  again  refer  to  the  group  of  oospora  in  treating  of 
actinomycosis. 

Special  mention  is  due  to  a  mucor  found  by  Paltauf  in  a  patient 
suffering  from  a  strange  affection  characterized  by  pharyngolaryngeal 
phlegmon,  pneumonia,  and  intestinal  ulcerations.  The  parasite  that 
had  given  rise  to  these  various  lesions  was  analogous  to  the  mucor 
corymbifer  whose  pathogenic  action  upon  animals  was  first  shown 
by  Lichtheim. 

The  pathogenic  properties  of  yeasts  and  of  oidium  albicans  will 
be  discussed  in  a  special  chapter. 

Finally,  more  highly  organized  parasites,  such  as  the  tricophytons, 
may  also  induce  suppurations.  Rosenbach  admits  seven  pyogenic 
species  of  them,  among  which  the  most  important  are  the  T.  menta- 
grophytes  in  man  and  in  the  horse,  and  the  T.  jelineum  in  the  cat 
and  in  children. 

It  is  well  to  add  that  the  majority  of  pyogenic  plants  are  capable 
of  producing  infectious  nodules  comparable  to  tuberculous  granula- 
tions. Such  is  the  case  with  regard  to  the  mucorinse,  the  aspergillus, 
the  saccharomycetes,  and  the  oidium.  These  various  parasites  will 
again  be  referred  to  in  the  chapter  on  pseudotuberculoses.  Some  of 
them  may  even  produce  genuine  tumor.  It  will  suffice  to  mention 
the  actinomyces.  Here,  then,  we  have  to  deal  with  a  series  of  facts 
which  establish  numerous  transitions  between  lesions  seemingly  very 
widely  apart — suppurations,  granulations,  and  neoplasms. 

5.  Pyogenic  Animal  Parasites. 

The  study  of  diseases  suffered  by  inferior  animals  has  drawn  the 
attention  of  observers  to  the  pathogenic  role  of  the  protozoa.  The 
presence  of  infusoria  and  flagellatse  in  the  suppurations  occurring  in 
man  has  long  been  noted.  The  balantidium  coli,  for  instance,  in  the 
suppurative  lesions  of  the  intestine;  the  trichomonas  vaginalis  in 
vaginal  suppurations  and  in  chronic  affections  of  the  digestive  canal. 
It  may  well  be  questioned,  however,  whether  these  parasites  are  not 
accidental  guests  by  no  means  pathogenic. 

The  arneba  coli,  an  animal  parasite,  is  held  by  many  observers 
to  be  the  agent  of  one  of  the  clinical  types  of  dysentery.  What  is 
of  more  direct  interest  for  our  subject  is  the  fact  that  this  parasite 
is  at  times  found  unassociated  with  other  organisms  in  hepatic 
abscesses  consecutive  to  dysentery.     With  Dr.  Peyrot,  the  author 


8UPPUBA  ri os.  193 

observed  a  c.'isc  of  this  kind,  [t  i  a  qua  tion,  however,  whether  the 
pus  did  not  at  some  time  contain  pyogenic  bacteria  which  had 
disappeared.  The  interesting  experiments  of  Marchoux  eem  to 
establish  that  the  amebaof  dysentery  is  really  capable  of  creating 
suppuration. 

Relative  Frequency  of  the  Various  Pyogenic  Agents. 

Anions  the  pyogenic  microbes  above  described  the  mosl  widely 
distributed  arc  the  staphylococci  and  the  streptococci.  I'  is  noi 
rare,  however,  to  find  several  bacteria  together  in  the  same  focus. 
Ogston  studied  sixty-nine  abscesses  and  detected  the  simultaneous 

presence  of  two  species  in  sixteen  instances.  Zuckermann  found 
records  of  495  bacteriological  examinations  of  ho1  abscesses.  In  70 
per  cent,  of  the  cases  the  staphylococcus  bad  been  found;  in  16  per 
cent,  the  streptococcus,  and  in  5.5  per  cent,  both  of  these  species. 
Then  followed  the  bacillus  pyogenes  fetidus,  the  bacillus  jii/utjcncs- 
tenuis,  the  tetragenus,  etc. 

The  association  of  several  pj^ogenic  microbes  seems  to  result  in 
an  aggravation  of  the  suppurative  phenomena.  Suppose  two  pyo- 
genic microbes  attenuated  to  such  an  extent  that  each,  injected  alone, 
produces  no  disturbance.  If  they  are  united,  the  result  of  their 
simultaneous  inoculation  is  the  formation  of  an  abscess. 

By  mixing  a  harmless  sample  of  the  staphylococcus  with  a  sapro- 
phyte or  an  attenuated  culture  of  streptococcus,  suppuration  is 
obtained.  By  study  of  the  purulent  focus,  however,  Trombetta 
recognized  that  the  focus  soon  became  monomicrobic.  The  staphy- 
lococcus prevailed,  and  soon  no  other  microbe  was  discoverable. 
This  fact  is  in  harmony  with  the  findings  of  clinical  observation.  A 
focus  may  at  first  contain  one  pyogenic  species,  and  at  the  end  of  a 
certain  period  of  time,  another.  Such  is  particularly  the  case  in 
otitis.  Whatever  may  have  been  the  microbe  found  at  the  beginning 
the  staphylococcus  is  almost  always  found  at  a  later  period.  Thus, 
there  are  microbes  which  start  a  suppuration  and  microbes  which 
maintain  it.  If  it  be  further  remembered  that  simple  saprophytes 
play  an  auxiliary  role  in  the  production  of  suppurative  phenomena, 
it  will  readily  be  understood  why  all  purulent  foci  should  be  protected 
against  external  germs,  even  apparently  inoffensive  ones. 

The  true  pyogenic  microbes,  notably  the  staphylococcus  and  the 
B.  coli,  are  abundantly  distributed  in  nature,  but  are  epiphytes 
rather  than  inhabitants  of  the  inorganic  world.    They  are.  therefore, 

13 


194  INFECTIO  US  DISEASES. 

found  mostly  in  crowded  neighborhoods,  in  hospital  wards,  and  in 
water  polluted  by  men  and  animals.  Once  thrown  into  the  external 
world,  these  pyogenics  would  soon  destroy  each  other  if  they  were 
not  protected  by  the  organic  materials  in  which  they  reside.  Pus, 
mucus,  fecal  matter,  etc.,  shield  them  against  causes  of  destruction, 
especially  against  the  influence  of  the  sun.  These  facts  must  be 
taken  into  serious  account,  since  in  experiments  it  is  the  resistance 
of  pyogenic  germs  derived  from  cultures,  and,  consequently,  placed 
under  less  favorable  conditions,  that  is  studied.  When  they  resist 
cosmic  agents  and  struggle  for  life  against  other  microbes,  the  pyo- 
genics gradually  lose  their  aptitude  to  thrive  in  living  organisms, 
become  attenuated,  and  finally  assume  the  rank  of  simple  sapro- 
phytes. This  is  what  happens,  for  instance,  with  the  strepto- 
coccus. 

The  staphylococcus  aureus  has  been  detected  in  the  air  (Fraenkel), 
dust,  soil  (Lubbert),  and  water  (Ullmann).  It  seems  to  be  more 
resistant  than  the  streptococcus.  The  latter  cannot  live  more  than 
five  days  in  sewer  water,  while  the  former  is  still  living  at  the  end  of 
twenty  days  (Strauss  and  Dubarry),  or  even  several  months  (Meade 
Bolton).  The  tetragenus  resists  eighteen  to  twenty  days.  The 
author  has  several  times  found  this  microbe  in  the  air,  a  fact  well 
in  harmony  with  its  frequent  presence  in  the  buccal  cavity. 

The  pneumococcus  is  far  more  delicate  than  the  preceding 
microbes.  Except  when  it  is  protected  by  the  mucus  of  expec- 
torations, it  becomes  attenuated  and  soon  perishes. 

The  proteus  vulgaris  and  mirabilis  and,  above  all,  the  bacillus  coli 
are  also  among  those  pyogenics  which  are  frequently  found  outside 
the  organism.  The  last-named  microbe  is  widely  distributed  and 
can  vegetate  in  water  for  months. 

These  microbes,  though  capable  of  living  in  the  external  world,  are 
nevertheless  parasites,  and  are  mostly  found  in  man  and  animals.  The 
S.  aureus  normally  vegetates  on  the  skin.  It  may  also  be  met  with 
in  the  mouth  and  in  the  nasal  mucus.  Escherich  has  detected  it  in 
the  stools  of  healthy  children,  a  result  due  to  contamination  of  the 
mother's  milk  at  the  nipple.  The  author  always  found  the  S.  albus 
in  milk  taken  under  ordinary  conditions,  while  this  secretion  was 
found  to  be  sterile  when  obtained  with  necessary  precautions. 

Streptococci  may  be  detected  in  the  same  localities  as  staphylo- 
cocci, but  the  former  are  inclined  to  abandon  the  exposed  parts  of 
the  organism.     They  are  seldom  encountered  in  the  skin.     Their 


SUPPURATION.  I!).-, 

seat  of  predilection  is  the  buccopharyngeal  cavity,  where  they  are 
constantly  present.  They  may  invade  the  digestive  trad  and  the 
genital  organs  of  women  in  the  lower  pari  of  the  vaginal  canal. 
This  last  localization  explains  their  frequency  in  the  lochia  of  women 

in  nowise  in  fee  led. 

The  tetragenus  and  pneumococcus  are  likewise  found  in  the  mouth. 
The  pneumococcus  is  met  with  in  aboul  one-fifth  of  all  subjects. 

No  wonder,  therefore,  thai  the  inoculation  of  saliv;i  into  the  rabbit, 
and  especially  the  mouse,  may  give  rise  to  a  speedily  fatal  septicemia. 
The  infection  thus  produced,  which  w;is  discovered  by  Pasteur  and 
well  studied  by  Sternberg,  is  due,  as  the  researches  of  Fraenkel  have 
established,  to  the  agent  of  fibrinous  pneumoni.i. 

The  B.  coli  is  also  widely  distributed  from  the  mouth  to  the  ami-. 
whence  it  enters  the  genital  organs.  It  is  also  found  in  all  animals. 
Hence  its  constant  presence  in  milk.  In  fact,  the  researches  of 
Wurtz  and  Leudet  tend  to  establish  that  the  lactic  ferment  is  nothing 
else  than  a  variety  of  colon  bacillus. 

From  this  brief  exposition,  it  may  be  seen  that  the  pyogenic 
microbes  are  everywhere  within  and  external  to  our  bodies.  This 
fact  points  to  a  rather  restricted  action  of  microbes  and  re-establishes 
the  role  of  the  organism  in  the  development  of  morbid  phenomena. 

We  are  thus  led  to  consider  how  and.  why  the  pyogenic  microbes 
invade  the  human  organism  and  how  they,  at  times,  become  virulent. 

Auxiliary  Causes  of  Suppuration. 

The  mode  of  development  of  a  suppuration  is  easily  accounted  for 
when  the  process  is  induced,  not  by  microbes  which  we  habitually 
harbor,  but  by  exalted  germs  of  diseased  animals  and  men.  The 
question,  then,  is  to  learn  how  this  primary  focus,  which  directly  or 
indirectly  contaminates  other  individuals,  originated.  In  many  cases 
suppuration  is  the  result  of  a  traumatism  which,  producing  a  solution 
of  continuity,  offers  an  entrance  to  these  microbes.  The  latter  find 
a  favorable  medium  in  the  altered  tissues  and  rapidly  develop. 

It  must  be  recognized,  however,  that  traumatism  does  not  always 
suffice  to  give  rise  to  suppuration,  even  in  the  absence  of  antiseptic 
precautions.  The  experiments  of  Garre,  Schimmelbusch.  and  Wash- 
nuith  established  that  pyogenic  micro-organisms  can  penetrate  into 
the  skin  of  man  and  animals  in  the  absence  of  the  slightest  cutaneous 
abrasion. 

At  the  present  day  it  is  a  matter  of  common  knowledge  that  a 


196  IXFECTIO  US  DISEASES. 

pyogenic  microbe  introduced  into  the  organism  docs  not  necessarily 
give  rise  to  symptoms.  It  may  be  rapidly  destroyed.  If,  in  other 
cases,  it  succeeds  in  doing  mischief,  it  is  owing  to  a  series  of  secondary 
causes,  soine  of  which  depend  upon  the  microbe,  others  upon  the 
invaded  organism. 

On  the  part  of  the  microbe  we  have  to  count  with  the  number, 
virulence,  and  mode  of  hit  roduction.  Fehleisen  long  since  recognized 
that  small  amounts  of  staphylococci  and  streptococci  may  be  injected 
beneath  the  skin  without  producing  any  lesion.  To  produce  an 
abscess  he  had  to  employ  1  c.cm.  of  the  culture.  If  5  c.cni.  were 
introduced,  the  animal  died  in  eighteen  or  thirty  hours  without  any 
suppurative  manifestation.  According  to  Odo  Bujwid,  suppuration 
does  not  appear  when  1,000,000,000  staphylococci  are  injected 
into  the  rabbit,  the  rat,  or  the  mouse.  It  may  happen  that  even 
8,000,000,000  are  insufficient  for  the  rabbit,  while  this  amount  is 
always  fatal  for  the  rat. 

The  value  of  these  figures  should  not  be  exaggerated.  The  results 
evidently  depend  upon  the  degree  of  virulence  of  a  given  sample, 
since  it  has  long  since  been  well  known  that  microbes  possess  no 
fixed,  definite  potency.  When  pyogenic  microbes  are  of  moderate 
virulence,  they  produce  pus;  when  highly  exalted,  their  inoculation 
causes  general  infection,  and  the  animal  speedily  succumbs  to  septi- 
cemia, and  microscopic  examination  reveals  no  appreciable  lesions 
in  the  cadaver.  On  the  other  hand,  when  they  are  too  attenuated, 
they  often  prove  incapable  of  giving  rise  to  the  slightest  lesion,  even 
though  they  are  introduced  in  considerable  numbers.  The  results 
vary  not  only  with  the  number  and  the  degree  of  virulence  of  the 
microbes,  but  also  with  the  mode  of  entrance.  Experimenting  upon 
rabbits,  Herman  discovered,  for  instance,  that  the  peritoneum  is 
twenty  times  more  resistant  than  other  parts  to  inoculations  of 
staphylococcus. 

When  directly  injected  into  the  blood,  the  pyogenic  microbes 
become  localized  in  various  organs  and  there  produce  purulent  foci. 
These  localizations  may  be  favored  by  visceral  lesions.  If,  for 
instance,  the  cardiac  valves  are  the  seat  of  traumatism,  an  ulcerative 
endocarditis  is  obtained ;  if  a  fracture  has  been  produced,  the  result 
will  be  an  osseous  suppuration.  It  is  possible  to  thus  create  artifi- 
cially points  of  fixation  for  the  agents  in  circulation.  Inspired  by 
this  fact,  Dr.  Fochier  attempted  to  create  aseptic  foci  designated  by 
the  name  of  abscesses  of  fixation.     In  his  opinion,  these  foci  were 


SUPPURATION.  197 

calculated  60  attract  the  microbes  to  those  poinl    where  they  would 

do  little,  if  any,  harm  to  the  organic m, 

Tissues  in  active  growth  may  likewise  represenl  point*  of  attrac- 
tion for  agents  in  circulation,  [ntravenous  injection  of  pyogenic 
microbes  may  induce  osteomyelitis  in  young  animal  .  a  ha  been 
shown  by  Etodet  experimenting  with  the  staphylococcus,  and  by 
Courmont  and  Jaboulay,  and  Lannelonge  and  Achard  with  the 
streptococcus. 

Role  of  Nervous  Alterations.  Simple  seel  ion  of  the  sciatic  n< 
without  inoculation  of  microbes  beneath  the  skin,  is  no1  followed  by 
trophic  ulcerations,  at  least  in  the  rabbit.  Such  is  not  the  case  with 
the  guinea-pig.  In  this  animal  a  gangrenous  edema  of  the  lower 
segments  of  the  limb  of  the  operated  side  supervenes  some  time  after 
the  excision  of  the  nerve.  The  tissues  swell  uwd  are  infiltrated  with 
pus,  then  disintegrate  and  leave  the  skeleton  denuded.  The  animal 
finally  dies.  The  fact  is  that  the  ulcerations  produced  by  the  wound 
upon  the  surface  of  the  skin  served  as  portals  of  entrance  to  the 
microbes,  and  the  germs  rapidly  multiplied  in  those  tissues  whose 
vitality  was  diminished  and  gave  rise  to  extended  injury. 

The  sciatic  is  a  mixed  nerve — motor,  sensory,  and  vasomotor — 
and  certain  of  its  fibres  seem  to  have  antagonistic  actions  upon  a 
local  infection.  In  order  to  prove  the  role  devolved  upon  the  various 
parts  of  the  nervous  system,  it  was  necessary  to  operate  upon  nerves 
performing  a  special  function.  I  therefore  first  studied  the  influence 
of  the  sympathetic  nerve. 

Brown-Sequard  long  since  had  established  experimentally  that 
section  of  the  great  sympathetic  favored  the  healing  of  wounds. 
Operating  upon  rabbits,  the  author  introduced  from  six  to  seven 
drops  of  a  streptococcus  culture  into  the  two  ears  at  the  same  point 
— i.  c,  in  the  middle  portion,  a  little  to  the  inside  of  the  central 
artery.  Immediately  after  the  inoculation  the  author  extirpated 
the  superior  cervical  ganglion  on  one  side.  At  the  end  of  twenty-four 
hours  the  operated  ear  was  found  hot  and  infiltrated  with  serum. 
The  inflammation  increased  and  reached  its  maximum  toward  the 
third  or  fifth  day.  From  this  moment  onward  the  aspect  of  the  two 
ears  completely  changed.  On  the  operated  side  the  lesions  resolved : 
on  the  intact  side  they  were  aggravated.  Toward  the  sixth  or 
eighth  day  the  nerveless  ear  resumed  its  normal  appearance,  while 
on  the  intact  side  the  lesions  grew  worse,  infiltration  being  enormous, 
abscesses  and  phlyctenule  having  developed,  as  a  result  of  which  a 


1 98  IXFECTIO  US  DISEASES. 

part  of  the  ear  sloughed  and  perished.  The  edematous 'infiltration 
generally  disappeared  toward  the  fifteenth  day,  persisting,  in  some 
instances,  for  twenty  and  even  fifty  days. 

In  these  comparative  experiments  section  of  the  sympathetic  nerve 
produces  a  double  effect.  It  gives  rise  to  congestion  in  the  operated 
ear,  and  to  anemia  in  the  intact  ear.  The  results  thus  become 
extremely  clear  owing  to  the  production  of  contrary  vasomotor 
modifications  on  the  two  sides. 

These  experimental  facts  remind  us  of  certain  clinical  observations. 
It  is  well  known  that  heat  is  emploj^ed  to  heal  certain  suppurative 
inflammations.  Active  congestion,  whether  produced  by  hot  appli- 
cations or  by  vasomotor  dilatation  of  the  arteries,  favors  recovery. 
It  may,  therefore,  be  concluded  that  active  congestion  is  favorable 
to  the  healing  of  a  local  lesion,  while  passive  congestion  renders  such 
lesion  more  serious  and  tends  to  produce  gangrene.  Similarly,  in  a 
cardiac  patient  in  the  stage  of  asystole,  the  slightest  lesion  results 
in  suppuration  or  sphacelation.  Finally,  suppression  or  diminution 
of  the  blood  supply,  as  is  realized  by  ligation  of  arteries,  favors  the 
development  of  local  lesions. 

The  influence  of  sensory  nerves  upon  the  development  of  suppu- 
ration can  easily  be  demonstrated  by  sectioning  the  amiculocervical 
nerve  of  a  rabbit  and  injecting  streptococci  beneath  the  skin  of  both 
ears.  In  order  to  obtain  clear  results,  use  should  be  made  of  an 
agent  of  moderate  power  which  gives  rise  only  to  a  small,  circum- 
scribed abscess  on  the  intact  side.  The  ear  deprived  of  the  nerve 
becomes  the  seat  of  an  intense  lesion — i.  e.,  a  very  marked  edema, 
phlyctenular  filled  with  a  serous  fluid,  and  abscesses,  which  may 
result  in  mutilation  or  perf oration  of  the  organ. 

Role  of  Previous  Local  Lesions.  The  presence  of  foreign  bodies 
in  a  wound  exercises  a  harmful  influence  upon  the  evolution  of  the 
process.  This  fact  is  one  of  those  proved  beyond  all  doubt  by  clinical 
observation.  In  many  cases  the  seemingly  endless  process  of  sup- 
puration has  been  abruptly  stopped  by  the  extraction  of  a  piece  of 
cloth,  a  fragment  of  a  bullet,  or  a  splinter. 

The  harmful  influence  of  caustic  or  irritant  substances  upon  inflam- 
matory processes  is  more  marked.  The  author  has  tried,  with  Dr. 
Josue,  the  effect  of  trimethylamin  and  of  carbolic  acid.  With  an 
amount  of  colon  bacillus  sufficient  to  produce  only  a  small  abscess 
in  the  controls,  half  a  gram  of  trimethylamin  was  injected  beneath 
the  skin  of  the  thigh  of  a  rabbit .     The  result  was  a  phlegmon  invad- 


SUPPURATION.  199 

ing  the  cellular  (issue  of  the  abdomen,  The  effeel  of  carbolic  acid 
is  even  more  manifest.  This  antiseptic  ub  tance,  far  from  com- 
bating infectioD  and  preventing  suppuration,  favor  them.  Having 
injected  subcutaneously,  as  above,  a  solution  of  5  eg.  of  carbolic  acid 
in  I  c.cm.  of  water,  then  0.5  c.cm.  of  a  culture  of  colon  bacillus  in 
bouillon,  we  noticed  the  production  of  an  enormous  diffuse  phlegmon 
infiltrating  the  whole  thigh  and  the  lower  half  of  the  abdomen.  It, 
however,  only  2  eg.  of  carbolic  acid  is  injected,  no  resull  what 
is  obtained.  This  is  a  fresh  demonstration  of  the  harmful  action  of 
strong  antiseptics. 

This  noxious  influence  of  chemical  substances  upon  the  vitality 
of  tissues  is  equally  exercised  by  disease.  The  (issues  already  altered 
by  a-  morbid  process  are  exposed  to  the  invasion  of  pyogenic  microbes. 
It  will  suffice  to  remember  the  purulent  foci  developing  in  neoplasms 
or  in  the  lungs  during  a  pneumonia  or  tuberculosis.  The  importance 
of  these  secondary  infections  is  well  known,  as  they  play  a  consider- 
able role  in  the  production  of  cavities  and  explain  the  hectic  phe- 
nomena observed  in  the  third  stage  of  consumption. 

Influence  of  the  General  State.  Individual  predisposition  and 
resistance  largely  depend  upon  the  general  state  of  the  organism. 
It  is  an  undoubted  fact  that  suppuration  is  more  liable  to  develop 
in  certain  subjects  than  in  others.  The  slightest  abrasion  in  them 
occasions  an  abscess  or  a  phlegmon.  Even  without  any  solution  of 
continuity,  a  contusion  or  friction  suffices  to  permit  the  penetration 
of  germs.  In  other  cases,  in  the  absence  of  any  appreciable  cause, 
cutaneous  suppurations,  acne,  abscesses,  furuncles,  and  anthrax 
appear,  and  sometimes  repeatedly. 

These  transitory  or  permanent  predispositions  depend  upon  either 
a  diathetic  condition,  an  inherited  or  acquired  mode  of  nutrition,  or 
a  series  of  causes  the  influence  of  which  has  been  conclusively  estab- 
lished by  numerous  clinical  and  experimental  facts.  Such  are  over- 
work, exposure  to  cold  and  heat,  starvation,  cachexias,  and,  above 
all,  intoxications. 

We  have  an  interesting  illustration  of  this  fact  in  mercurial  stoma- 
titis. The  buccal  lesions  are  not  due  to  the  elimination  of  mercury. 
On  the  contrary,  the  mercury  acts  by  creating  a  morbid  predispo- 
sition and  by  diminishing  the  resistance  of  the  tissues.  Hence,  the 
rapid  development  of  pyogenic  microbes  and  the  exaltation  of  their 
virulence,  which  explains  why  mercurial  stomatitis  may  become  con- 
tagious.    Diday  reported  the  history  of  a  man  who  communicated 


200  INFECTIOUS  DISEASES. 

this  affection  to  his  wife.     Transmission  of  exalted  bacteria  had 
occurred  in  this  case. 

The  cutaneous  manifestations  of  bromism  and  iodism  are  likewise 
accounted  for  by  the  development  of  pyogenic  microbes  present  upon 
the  surface.  The  phenomena  are,  however,  more  complex  in  this 
instance,  as  the  concomitant  gastrointestinal  disturbances  must  also 
be  taken  into  account.  In  fact,  Dr.  Fere  has  established  that  these 
infectious  manifestations  may  be  diminished  and  suppressed  by 
means  of  intestinal  antisepsis. 

Those  chemical  substances  which  diminish  the  alkalinity  of  the 
blood  seem  to  favor  suppuration;  but  the  results  are  not  sufficiently 
conclusive.  On  the  other  hand,  some  authorities  maintain,  though 
their  conclusions  have  often  been  contradicted,  that  the  administra- 
tion of  sodium  bicarbonate  for  some  length  of  time  renders  the 
animals  more  resistant  by  increasing  the  alkalinity  of  their  humors. 

There  is  a  group  of  substances  wrhich  favor  the  development  of 
pyogenic  agents.  We  refer  to  ferments.  The  author  has  shown 
that  the  attenuated  streptococcus  recovers  its  virulence  when  it  is 
injected  with  papain.  What  the  products  of  highly  organized  plants 
do,  microbic  products,  ferments,  and  ptomains  can  also  realize,  and 
even  more  readily.  Grawitz  has  thus  recognized  that  the  simulta- 
neous introduction  of  cadaverin  and  staphylococci  or  streptococci 
gives  rise  to  a  violent  phlegmon,  the  alkaloid  and  the  microbe  having 
powerfully  aided  each  other. 

The  resistance  of  the  organism  to  pyogenics  also  diminishes  as  a 
result  of  nutritive  disturbances  suffered  in  grave  diseases.  Con- 
valescents from  typhoid  fever,  for  instance,  often  develop  manifold 
suppurations,  abscesses,  and  furuncles,  which  may  adequately  be 
accounted  for  by  insufficient  nutrition  of  the  subject. 

Finally,  it  is  interesting  to  note  that  quantitative  modifications 
of  the  blood  seem  to  be  without  influence.  Even  abundant  and 
repeated  general  bleeding  is  ineffective. 

Generalization  of  Suppurating  Lesions. 

We  have  thus  far  studied  the  causes  which  explain  the  develop- 
ment or  aggravation  of  a  purulent  focus.  It  is  evident,  however, 
that  suppuration  does  not  always  remain  circumscribed,  and  that 
the  microbes  may  emigrate  and  give  rise  to  visceral  colonies.  Why 
are  not  the  germs  which  enter  the  circulation  destroyed  by  the 
protective  organs  ?     Rhine  justly  attributes  this  failure  to  a  general 


SUPPURATION.  201 

decline  of  the  organism,  due  to  the  effect  of  microbic  prod 
mated  at  the  primary  Focus.    As  microbic  3ecretioi  with  the 

samples  employed  and  the  aptitude  of  the  organism  to  neutralize  the 
toxins  differs  from  one  individual  to  another,  il  is  readily  conceived 
why  the  process  sometimes  remains  local  and  al  others  becomes 
generalized. 

Of  the  microbes  which  pass  into  the  general  circulation,  some  are 
destroyed  l>y  Hie  leucocytes,  some  are  eliminated,  and  others  remain 
in  the  tissues.  The  elimination  is  mainly  effected  by  the  kid] 
and  the  skin.  Brunner,  Eiselsberg,  Gaertner,  Tizzoni;  Preto,  Nan- 
notti,  and  Baciocchi  have  detected  the  staphylococcus  in  the  urine 
and  sweat  in  cases  of  general  infect  ions,  even  in  benign  suppurations. 
The  latter  instance  is  of  great  interest,  as  it  tend-  to  prove  that 
pyogenic  microbes  easily  penetrate  into  the  organism,  bul  are  quickly 
destroyed  or  eliminated.  Elimination  through  the  emunctories 
seems  to  be  achieved  without  any  inconvenience  to  the  eliminating 
organs.     It  is  a  true,  natural,  therapeutic  procedure. 

Such  is  not  always  the  course  of  events,  however.  The  microbes 
that  have  found  access  to  the  organism  are  not  invariably  destroyed 
or  eliminated,  and,  if  very  virulent,  they  then  are  capable  of  causing 
a  fatal  septicemia.  If  they  are  less  active  they  create  purulent  foci, 
which,  according  to  their  number  and  locality,  may  resolve  or  prove 
fatal.  The  formation  of  visceral  foci  may,  therefore,  be  considered 
as  a  last  defensive  measure  on  the  part  of  the  organism.  Numerous 
clinical  facts  demonstrate  that  in  puerperal  women,  for  example,  the 
development  of  a  phlebitis  or  of  a  periuterine  phlegmon  coincides 
with  amelioration  of  the  puerperal  fever  and  a  retrogression  of  alarm- 
ing phenomena.  The  localization  may  become  very  grave  of  itself. 
but  the  immediate  accidents  are,  in  part,  avoided. 

Non-microbic  Suppurations. 

We  have  seen  that  most  of  the  known  microbes  may.  under  cer- 
tain circumstances,  give  rise  to  the  formation  of  a  purulent  focus. 
We  now  come  to  the  question  whether  suppuration  is  ever  possible 
without  the  intervention  of  animate  agents.  ITueter  and  his 
ciples  were  the  first  to  experiment  with  aseptic  substances  by 
injecting  a  certain  amount  of  a  solution  of  silver  nitrate  and  of 
zinc  chloride  into  the  subcutaneous  cellular  tissue.  No  abscess  fol- 
lowed, and  the  authors  concluded  that  there  is  no  pus  without 
microbes. 


202  IXFECTIO  US  DISEASES. 

In  1883  Straus  published  the  result  of  forty  experiments  made 
upon  rabbits,  guinea-pigs,  and  rats.  He  had  introduced  beneath  the 
skin  the  most  varied  substances,  such  as  croton  oil,  sterilized  water, 
mercury,  etc.  and  in  no  case  did  he  observe  suppuration,  save  when 
microbes  had  accidentally  penetrated.  Analogous  results  were  ob- 
tained by  other  experimenters.  In  1885  the  Medical  Faculty  of 
Berlin  made  this  a  competitive  question.  Klemperer  secured  the 
prize.  In  his  various  experiments  intense  inflammation,  or  serous 
exudation,  or  even  coagulation  necrosis  was  observed,  but  there  was 
no  pus.  Zuckermann  experimented  with  no  less  than  thirty-one 
substances,  and  never  observed  pus  without  microbes. 

So  many  experiments  performed  by  able  scientists  would  seem 
sufficient  to  settle  the  question,  but  we  shall  now  cite  another  series 
of  researches  leading  to  a  diametrically  opposite  conclusion.  Riedel 
obtained  aseptic  suppuration  by  injecting  mercury  into  the  knee- 
joint  of  a  rabbit,  and  Cohnheim,  by  introducing  croton  oil  beneath 
the  skin  of  a  dog.  Councilman  took  up  the  question  and  resorted 
to  a  very  ingenious  procedure.  The  substance  under  study  was 
placed  in  a  glass  tube  which  was  then  closed  at  both  ends.  The 
tube  was  inserted  beneath  the  skin  of  the  animal  and  was  broken 
when  the  small  wound  had  cicatrized.  By  this  method,  the  employ- 
ment of  a  mixture  of  croton  oil  and  olive  oil  produced  pus  in  the 
rabbit  without  any  micro-organisms. 

We  owe  one  of  the  best  works  on  this  subject  to  Grawitz  and  Bary. 
These  authors  demonstrated  that  it  is  hardly  possible  to  produce  in 
rabbits  and  guinea-pigs  suppuration  without  microbes.  The  case  is 
different  with  the  dog.  A  5  per  cent,  solution  of  silver  nitrate  and 
concentrated  ammonia  were  found  capable  of  giving  rise  to  aseptic 
abscess.  Terebinthine  is,  however,  the  substance  endowed  with  the 
most  marked  pyogenic  properties.  Nathan  failed  to  prove  this  action 
owing  to  the  insufficient  amount  (0.6  c.cm.)  employed  by  him. 

As  has  well  been  remarked  by  Rosenbach,  the  fundamental  short- 
coming of  the  first  experimenters  is  the  generalization  of  the  results 
obtained  with  one  animal  species.  Various  substances,  particularly 
mercury  and  terebinthine,  are  pyogenie  for  the  dog,  while  they  are 
only  phlogogenic  for  the  rabbit  and  the  guinea-pig.  Other  experi- 
menters subsequently  confirmed  this  distinction. 

The  problem  may  now  be  held  to  have  been  solved.  In  the  absence 
of  microbic  intervention,  suppurations  may  develop  by  the  action 
of  chemical  substances.     The  list  of  such  substances  has  been  con- 


SUPPURATION.  203 

siderably  augmented  by  the  latesl  contributions  upon  thu  Bubject. 
The  higher  the  dose  and  the  greater  the  concentration  of  these  bud- 
stances,  the  more  energetic  is  their  action.  Hence,  the  possibility 
of  varying  their  effects  so  as  to  obtain  s  simple  sero  anguinolenl 
exudate,  an  abscess,  :i  phlegmon,  or  &  slough. 

Researches  have  further  demonstrated  thai  the  character  of  pue 
-of  chemical  origin  is  the  same  as  thai  of  pus  of  bacterial  origin.1 

Lastly,  Poliakoff  has  discovered  the  very  interesting  facl  thai  the 
more  slowly  the  pyogenic  chemical  Bubstances  are  introduced  into 
the  tissues,  the  better  they  act.  T<>  demonstrate  this,  he  introduced 
small  capsules  of  collodion  containing  five  drop-  of  turpentine  oil 
beneath  the  skin  of  a  rabbit.  A  large  abscess  was  produced,  although 
only  a  part  of  the  amount  introduced  had  had  time  to  diffuse.  The 
counterexperiment  consisted  in  injecting  five  drop.-  a1  once.  The 
result  was  slight  tumefaction  without  suppuration. 

Pyogenic  Properties  of  Microbic  Products.  Researches  pursued 
by  a  number  of  authorities  have  demonstrated  thai  subcutaneous 
inoculation  of  sterilized  cultures  of  bacteria  may  give  rise  to  suppu- 
ration. This  action  is  in  part  due  to  bacterial  protoplasm  and  in 
part  to  soluble  substances. 

A  great  number  of  experiments  have  shown  the  presence  of  pyo- 
genic material  among  the  secretory  products  of  the  staphylococcus 
•aureus.  Leber  has  succeeded  in  extracting  from  its  cultures  a  crys- 
tallizable  body,  soluble  in  alcohol,  and  possessing  inflammatory  and 
necrosing  power  in  the  highest  degree.  The  author  designates  it  urn  ler 
the  name  ■phlogosin  and  distinguishes  it  from  the  non-toxic  alkaloids 
found  by  Brieger  in  pus.  No  analytical  study  has  been  undertaken 
related  to  substances  in  cultures  of  other  pyogenic  microbes. 

The  Non-microbic  Suppurations  in  Clinical  Observations.  It  was 
for  some  time  believed  that  the  study  of  non-microbic  suppurations 
was  only  of  theoretical  interest.  It  is  at  present  known  that  non- 
microbic  suppurations  may  also  occur  in  man.  The  pus  in  chronic 
salpingites  often  contains  no  bacteria.  The  same  is  true  as  regards 
hepatic  abscesses,  as  has  been  pointed  out  by  Kartulis,  Laveran. 
Netter,  and  Peyrot.  Since  these  first  contributions  thiriy-eight 
observations  have  been  published  concerning  non-microbic  suppura- 
tions of  the  liver.2   Brouardel  and  Josue  have  reported  the  observa- 

1  Poliakoff.  Ueber  Eiterung  mit  und  olme  Mikroorganismen  Centralb.  f.  Bakt., 
Bd.  xviii.  p.  33,  1S95. 

2  Longuet.     La  sterilite  dans  le  pus  des  a  bees  du  foie.     La  Presse  rued..  1S95.  p.  99. 


204  INFECTIOUS  DISEASES. 

tion  of  a  cerebral  abscess  in  which  the  pus  was  tree  from  microbes. 
Tuffier,  operating  upon  a  caleulopyelonephritis,  found  a  litre  of  fetid 
pus  containing  no  bacteria  cultivable  by  the  ordinary  procedures. 
In  the  majority  of  instances  in  which  suppuration  is  sterile,  the  puru- 
lent focus  gives  rise  to  no  notable  disturbance  and  arouses  no  general 
reaction. 

Several  hypotheses  have  been  advanced  to  explain  the  aseptic 
character  of  certain  purulent  foci.  Only  one  seems  to  the  author 
acceptable.  The  probabilities  are,  to  say  the  least,  that  the  focus 
has  primarily  been  fertile — viz.,  that  it  developed  under  the  influence 
of  the  ordinary  pyogenic  germs,  which  subsequently  disappeared. 
This  view  is  supported  by  certain  clinical  and  experimental  facts. 
The  author  has  reported  two  such  experiments  pursued  with  Dr. 
Josue.  Half  a  cubic  centimetre  of  a  culture  of  proteus  vulgaris  was 
injected  into  the  cellular  tissue  of  the  thigh  of  a  rabbit.  A  month 
later  the  animal  was  killed.  The  necropsj^  revealed  a  circumscribed 
abscess  the  size  of  an  almond.  The  pus  of  this  abscess  contained 
no  microbes  visible  under  the  microscope.  It  produced  no  growth  in 
the  various  artificial  culture  media.  Inoculated  into  the  cellular 
tissue  of  a  rabbit,  it  caused  no  lesion.  The  second  experiment  was 
made  upon  a  rabbit  with  B.  coli  with  analogous  results. 

It  may  be  concluded,  therefore,  that  when  a  suppuration  is  pro- 
duced in  an  animal  in  such  a  manner  as  to  allow  no  communication 
with  the  external  air,  the  microbes  introduced  become  gradually 
attenuated,  are  no  longer  cultivable,  and  can  no  longer  overcome  the 
resistance  opposed  to  them  by  the  living  organism.  Diminution  and 
disappearance  of  virulence,  diminution  and  disappearance  of  vege- 
t  ability,  degeneration  and  dissolution  are  the  successive  phases 
through  which  pyogenic  microbes  pass  in  a  closed  focus. 

Physical  and  Chemical  Characters  of  Pus.  The  characters  of  pus 
vary  notably  from  one  sample  to  another.  Phlegmonous  pus,  which 
is  always  taken  as  typical,  is  an  opaque,  creamy,  yellowish-white, 
odorless  fluid.  On  ebullition,  it  smells  like  milk.  Its  taste  is  rather 
sweet,  which  is  due  to  the  presence  of  a  great  amount  of  soap  masking 
the  salty  flavor  of  sodium  chloride. 

Under  certain  circumstances  pus  occurs  as  a  thick  mass,  resem- 
bling certain  soft  cheeses.  Such  caseous  pus  is  frequent  in  animals, 
particularly  in  small  rodents,  such  as  rabbits  and  guinea-pigs,  em- 
ployed in  laboratories.  In  other  cases,  pus  is  thin.  The  serous 
portion  is  partially  separated  from  the  solid  elements  which  are  found 


SUPPURATION.  205 

in  the  form  of  coagula.     It  Is  often  contaminated  with  produd 
putrid  fermentations.     H   then  becomes    aniou  .  gangreno 
chocolate-brown  color,  and  contain*  detritu    of  necrotic  I 
times  gas,  and  exhales  a  nauseating  odor. 

Rosenbach  supposed  thai  the  color  of  pui  was  related  to  the  nature 
of  the  pyogenic  agenl  thai  the  staphylococcus  aureus  was  con- 
cerned in  the  formation  of  yellow  pus,  and  thai  the  S.  albu 
found  in  the  while  variety.  This  idea  does  nol  seem  to  be  correct, 
and  we  need  nol  wonder,  since  the  S.  aureus  produces  no  pigment 
when  it  is  protected  from  air,  as  is  the  ease  with  foci  of  suppuration. 

It  is  not  practicable,  therefore,  to  determine,  by  examining  a 
sample  of  pus,  whal  pyogenic  agenl  is  concerned,  or  to  tell  whether 
the  pus  is  actually  inhabited  by  living  microbes  or  is  free  from  bac- 
teria. Cultures  are  indispensable.  An  except  ion  may  be  made  only 
with  suppurations  caused  by  the  pneumococcus.  These  are  remark- 
able for  their  thickness,  due  to  the  great  amount  of  fibrin  present, 
and  for  their  greenish  color.  Hence,  the  possibility  to  declare  their 
origin  at  first  sight. 

Microscopic  examination  may  reveal  the  origin  of  a  suppuration 
by  the  various  elements  present,  such  as  glandular  cells,  fibres  of 
connective  or  elastic  tissue,  crystals  of  fatty  acids,  cholesterin,  hema- 
toidin,  calcareous  grains,  and,  finally,  microbes. 

Certain  pathological  secretions  resemble  pus.  Such,  especially,  i- 
the  concrete  mucus  found  in  endometritis;  then  the  steatomatous 
fluid  of  sebaceous  cysts  and,  to  a  certain  extent,  the  contents  of 
syphilitic  gummata.  Error  in  these  cases  may  easily  be  avoided. 
However,  the  chyliform  exudates  of  serous  membranes,  notably  in 
the  pleura,  peritoneum,  ami  tunica  vaginalis,  have  long  been  mis- 
taken for  pus.  These  are  probably  cases  of  old  purulent  foci  in 
which  the  morphological  elements,  microbes,  and  animal  cells  have 
undergone  fatty  degeneration.  There  remains  only  an  emulsion  of 
fat,  the  nature  of  which  may  readily  be  determined  by  microscopic 
examination  or  chemical  analysis.     . 

In  genuine  pus  the  microscope  reveals  the  presence  of  characteristic 
cells,  formerly  designated  as  pyocytes.  It  is  at  present  possible  to 
differentiate  the  cells  and.  in  fact,  the  same  elements  are  found  in 
pus  as  in  the  blood.  Tus  contains  poly  nuclear  neutrophile,  eosino- 
phile,  and,  exceptionally,  basophile  leucocytes,  as  well  as  mononu- 
clears and  lymphocytes.  Finally,  there  are  found  two  orders 
degenerated  cells:  the  so-called  corpuscles  of  Gluge,  which  seem  to 


206  INFECTIO  US  DISEASES. 

be  made  up  of  an  agglomeration  of  disintegrated  cells,  having  under- 
gone fatty  degeneration,  and,  in  the  next  place,  large  spheroidal 
cells,  often  in  a  state  of  mucoid  degeneration,  and  derived  from  the 
fixed  cells  of  connective  tissue  and  from  endothelial  or  adipose  cells. 

These  various  cellular  elements  are  found  in  variable  proportions. 
The  polynuclear  neutrophiles  predominate  in  ordinary  pus.  Gonor- 
rheal pus  is  said  to  be  remarkable  for  the  great  abundance  of  eosin- 
ophiles  it  contains.  In  reality,  however,  these  cells  abound  only  at 
the  time  when  the  acute  phenomena  are  subsiding.  Their  appear- 
ance is  always  an  indication  of  recovery.  It  may  be  hoped  that 
further  advances  in  the  cytological  study  of  pus  will  furnish  data 
utilizable  in  clinical  observation.  Not  that  the  cellular  formula}  vary 
with  each  species  of  microbe ;  on  the  contrary,  they  seem  to  be  related 
rather  to  certain  groups  of  pathogenic  agents.  Thus  the  pus  pro- 
duced by  microbes  so  closely  related  as  are  those  of  variola,  varicella, 
and  vaccinia,  possesses  the  same  character.  In  all  three  instances  it 
is  remarkable  for  the  abundance  of  mononuclears  it  contains. 

Chemical  Characters  of  Pus.  From  what  has  been  said  regarding 
varieties  of  suppuration,  it  is  natural  to  conclude  that  pus  does  not 
always  possess  the  same  chemical  characters.  The  results  obtained 
by  analyses  cannot,  therefore,  have  a  general  bearing.  They  never- 
theless deserve  to  be  examined  in  detail. 

Pus  is  a  neutral  fluid,  at  times  alkaline,  seldom  acid.  Acidity, 
when  present,  is  clue  to  fatty  acids  and  notably  to  butyric  acid. 

Treated  with  nitric  acid,  pus  gives  an  abundant  precipitate  of 
albumin.  The  addition  of  ammonia  transforms  it  into  a  semisolid, 
translucent  mass,  similar  to  thick  mucus.  This  effect  is  referable 
to  the  action  exercised  upon  the  albumin  by  the  leucocytes  destroyed 
bjr  the  alkali. 

The  specific  gravity  of  pus  varies  from  1020  to  1040.  With 
phlegmonous  pus  it  varies  between  1031  and  1033.  When  left  to 
itself,  pus  does  not  coagulate,  because  it  contains  no  fibrin.  AVhen 
heated,  it  solidifies  at  about  167  F.  (75  C).  Allowed  to  stand,  pus 
separates  into  two  layers:  a  clear,  superficial  layer,  the  pus  serum, 
and  a  lower  opaque  layer,  which  contains  the  cellular  elements,  the 
pyocytes.  There  are  710  to  831  parts  of  serum  to  166  to  290  parts 
of  corpuscles.  These  figures  are  variable.1  The  chemical  analysis  of 
pus  corpuscles,  made  by  Hoppe-Seyler,  gives  the  following  figures: 

1  Ch.  Robin.  Lecons  sur  les  humeurs  normales  et  morbides  du  corps  de  l'liomme . 
Paris,  1874,  2d  ed.,  p.  376. 


SUPPURATION. 


207 


Organic  Substances  Oontainto  in  Owb  Hi  «>bbd  Pabti  01    Dm  Cbm*. 

i  II 

Proteids  l3»7fl  '  I 


Nuclein 

[llHolllMc  ::nli  .l.'ilirc:; 

Lccilin 

Fat 

Cholesterin 

Cerebrin 

Exl  paotive  substanceB 


34,207  [-68,588     67,389 

r  i    7.584 

,    '  '  (    7..V,, 

7,400  7,28:', 


5,199 
4,433 


LO,28  i 


Inorganic  Substances  Contains.  [N  Onb   Htwdbbd  Pasts  of  D       I 

N.,0.      .  .  • 

Ca3(Ph04)2      . 


Mg3(Ph04), 
Fe2(Ph04)2 
Ph04      . 

Na 
K 


0.205 
0.113 
0.106 
0.918 
0.068 
i  races 


The  pus  scrum  resembles  blood  serum  in  its  chemical  constitution. 
Some  authorities  have  even  gone  so  far  as  to  regard  the  two  fluid* 
as  identical.  It  has  been  objected  that  the  composition  of  pus  serum 
is  not  constant,  but  the  blood  serum  is  no  less  variable.  This  is 
clearly  demonstrated  by  the  following  figures : 


Serum  of  Blood 
(C.  Schmidt). 


Serum  of  Pus 

(Hoppe-Seyler) . 


Water  . 

Organic    substances 

Inorganic  substances 


I. 
917.15 
74.43 
8.42 


II. 

908.84 

82.59 

8.57 


I. 
913.70 
78.57 
7.73 


II. 

905.65 

86.58 

7.77 


Among  the  substances  found  in  pus  serum  the  most  important 
are  undoubtedly  the  albuminoids,  serin,  globulin,  albumose,  and.  in 
osseous  abscesses,  chondrin.  Much  stress  has  recently  been  laid  upon 
the  presence  of  ferments,  toxalbumins,  and  ptomains,  depending  in 
part  upon  the  multiplication  of  microbes.  Dr.  Achalme.  who  has 
made  an  admirable  study  of  ferments  contained  in  pus.  notes  the 
presence  of  lipase,  amylase,  trypsin,  casease,  a  zymase  liquefying 
gelatin,  another  decomposing  peroxide  of  hydrogen,  ami.  finally,  oxi- 
dase. The  last-named  ferment  is  always  very  abundant.  Sucrase 
inulase,  emulsin,  lactase,  and  plasmase  are  always  absent.  These 
various  ferments  are  not  produced  by  microbes,  since  they  are  also 
found  in  aseptic  abscesses.  Dr.  Achalme  is  inclined  to  assign  their 
origin  in  the  leucoevtes. 


208  IXFECTIO  US  DISEASES. 

Development  and  Evolution  of  Purulent  Foci. 

Suppuration  cannot,  in  the  author's  opinion,  be  held  to  be  a  reac- 
tion aroused  directly  by  chemical  or  animate  pyogenic  agents.  The 
mechanism  is  more  complex,  and  involves  two  distinct  acts.  The 
pyogenic  agents  first  give  rise  to  a  necrosis,  a  primary  mortification 
of  tissues.  The  parts  thus  altered  become  a  cause  of  secondary  irri- 
tation which  is  expressed  by  the  production  of  round  cells,  of  which 
some  originate  on  the  spot  and  others  migrate  from  the  vessels. 

When  pyogenic  toxins  or  a  chemical  substance,  like  turpentine,  are 
introduced  into  the  subcutaneous  cellular  tissue,  the  first  act  of 
pyogenesis  is,  as  has  been  shown  by  Bardenheuer  with  turpentine, 
a  cellular  necrosis.  A  reaction  then  becomes  manifest.  This  is  the 
second  act  of  the  process.  Around  the  necrosed  region  the  cells  swell 
and  proliferate.  At  the  same  time  the  vessels  dilate  and  exude  a 
serosity,  while  the  leucocytes  migrate  from  the  blood  current  and 
take  up  a  position  between  the  necrosed  and  the  inflamed  parts. 
Some  of  the  new  cells,  however,  die  and  remain  in  the  central  zone 
of  the  focus.  We  may  admit,  then,  with  Lemiere,  that,  as  a  rule, 
every  suppurative  focus  consists  of  three  zones:  a  central  necrosed 
zone:  a  middle  zone,  characterized  by  an  infiltration  of  leucocytes, 
and  a  peripheral  zone  made  up  of  fixed  cells  which  proliferate  and 
tend  to  encyst  the  lesions. 

Among  these  phenomena  the  arrival  of  leucocytes  is  a  most  inter- 
esting one.  It  is  known  that  the  blood  normally  contains  about 
6000  leucocytes  per  cubic  millimetre,  or  30,000,000,000  for  the  five 
kilograms  of  blood  of  the  human  body.  In  phlegmonous  pus 
125,000  pyocytes  per  cubic  millimetre  are  counted,  or  125,000,000,000 
per  kilogram  (one  litre).  In  some  cases  suppuration  amounts  to 
500  or  even  1000  c.cm.  in  twenty-four  hours.  Taking  the  lesser 
figure,  500  c.cm.,  we  see  that  the  focus  discharges  60,000,000,000 
round  cells,  the  greater  part  of  which  is  represented  by  leucocytes. 
This  is  nearly  twice  as  much  as  the  number  of  leucocytes  contained 
in  the  total  amount  of  blood.  It  is  to  be  noted  that  the  phenomena 
of  diapedesis  are  prepared  and  preceded  by  an  increased  leucocytosis. 
The  blood  of  an  individual  suffering  from  suppuration  is  found  to 
contain  15,000  to  20,000  leucocytes  per  cubic  millimetre;  in  some 
cases  this  figure  reaches  36,000. 

It  now  remains  for  us  to  learn  how  this  increased  production  of 
white  corpuscles  is  effected.     It  probably  depends  upon  the  microbic 


SUPPURATION.  209 

and  cellular  secretions  occurring  in  the  focus  of  suppuration.     In 
fact,  it  has  been  established  thai  the  secretions  of  certain  microbes 
:iii(l  the  proteins  contained  in  their  protoplasm  excite  leuc 
(Buchner),    In  non-niicrobic suppurations  this  rdle  of  excitanl  musl 
devolve  on  the  products  of  cellular  destruction. 

The  microbic  or  cellular  products  thus  originating  in  the  affected 
parts  act  probably  upon  the  organs  in  which  the  leucocytes  are 
formed — the  bone-marrow,  lymphatic  glands,  spleen,  and,  in  children, 
the  thymus.  They  induce  proliferation  in  distanl  parte  ae  they  do 
in  the  main  focus.  Nutritive  and  proliferative  overactivity  may, 
perhaps,  account  in  pari  for  the  fever  of  suppuration. 

Cohnheim  had  already  noted  thai  the  leucocytes  could  not  emi- 
grate unless  the  vessels  were  dilated  and  the  circulation  slowed. 
After  these  white  corpuscles  have  passed  out  of  the  bloodves 
they  make  their  way  to  the  pyogenic  agents.  In  fact,  it  has  been 
demonstrated  that  sterilized  cultures  of  the  staphylococcus  aureus 
possess  the  property  of  attracting  the  migrating  cells.  If  a  number 
of  capillary  tubes  be  introduced  into  the  abdomen  of  a  frog,  some 
of  the  tubes  being  filled  with  sterilized  cultures  of  the  microbe  men- 
tioned and  others  with  water  or  bouillon,  the  latter  remain  un- 
touched, while  the  former  become  filled  with  numberless  leucocytes. 
The  products  of  organic  disassimilation  exercise  an  analogous  influ- 
ence and,  consequently,  the  cells  altered  by  pyogenic  substances 
become  a  new  source  of  attraction  for  the  leucocytes. 

Some  of  these  leucocytes,  when  in  contact  with  the  accumulated 
products  in  the  foci,  undergo  rapid  necrosis.  Others,  simply  irritated, 
proliferate  by  direct  division  of  the  nucleus.  "While  the  migrated 
leucocytes  are  at  work  the  fixed  cells  of  the  tissue  do  not  remain 
inactive.  The  old  experiments  of  Hoffmann  and  von  Recklinghausen 
tend  to  prove  this.  These  authors  irritated  the  cornea  of  an  animal 
and  then  placed  the  eye  or  the  entire  head  in  a  damp  chamber. 
After  some  time  they  found  an  accumulation  of  round  cells  at  the 
irritated  point.  Yon  Recklinghausen  has  likewise  seen  the  cells  of 
the  cornea  undergo  a  change  in  form  and  become  migrating  cells. 
Similar  modifications  have  been  described  in  the  cells  of  connective 
and  adipose  tissue,  and  in  those  of  serous  membranes  (Cornil  and 
Toupet).  According  to  Grawitz,  connective  tissue  cells  are  the  seat 
of  an  active  karyokinesis  and  are  transformed  into  mononuclear  and 
even  polynuclear  corpuscles.  Let  us  also  recall  the  recent  researches 
of  Ranvier  on  the  clasmatocytes,  those  large  connective  tissue  cells 

14 


210  IXFECTIO  US  DISEA  SES. 

which  represent  fixed  leucocjiies  and,  under  the  influence  of  inflam- 
mation, are  again  converted  into  white  corpuscles. 

The  respective  roles  of  fixed  and  wandering  cells  have  been  shown 
by  The  researches  pursued  by  Ribbert  with  the  staphylococcus,  and 
by  Kiener  and  Duclert  with  the  tetragenus. 

A  focus  of  necrosis  is  first  produced,  then  large  leucocj^tes  enter 
the  field,  which  process  takes  place  coincidently  with  a  proliferation 
of  fixed  cells.  These  various  cells  are  endowed  with  great  phagocytic 
activity.  Such  are  the  phenomena  observed  on  the  first  dajr.  On 
the  second  day  the  fixed  cells  become  the  seat  of  karyokinesis  and 
begin  the  process  of  repair.  At  this  time  leucocytes  of  the  smaller 
variety  arrive.  If,  however,  the  quantity  of  microbes  introduced  is 
quite  considerable,  many  phagocytes  die,  and  some  of  them,  as  well 
as  the  microbes  yet  at  large,  are  seized  and  ingested  by  the  macro- 
phages— i.  e.,  by  the  large  mononuclear  cells  derived  from  the  con- 
nective tissue  cells.  The  phagocj^tic  role  of  fixed  cells  is  especially 
marked  from  the  fourth  day  onward.  At  this  period  the  enveloping 
or  pyogenic  membrane  becomes  vascularized,  granulations  develop 
rich  in  giant  cells,  which  continue  the  work  of  phagocytosis,  and  in 
white  cells,  which  become  the  future  clasmatocytes. 

According  to  Ribbert,  the  round  cells  defend  the  organism  not  only 
by  ingesting  the  microbes,  but  by  forming  a  barrier  around  the 
virulent  focus  and  establishing  a  sort  of  vital  competition  with  the 
pathogenic  agents.  The  latter  succumb  because  their  supply  of 
nutrient  elements  and  oxygen  is  cut  off  and  they  are  poisoned  by 
their  own  noxious  substances. 

Thus,  while  on  the  one  hand  the  microbes  are  ingested  and  de- 
stroyed, on  the  other  the  cells  die.  If  the  dead  cells  are  not  very 
numerous,  the  macrophages  pick  them  up  and  remove  them  as  well 
as  the  bacteria  contained  in  them  (scavengers).  No  suppuration  is 
produced  and,  after  a  certain  time,  the  lesion  is  completely  healed. 
If,  on  the  contrary,  the  number  of  dead  cells  is  considerable,  the 
cadavers  accumulate  in  the  focus,  and  thus  is  constituted  the  puru- 
lent collection. 

In  most  cases  the  abscess  opens  externally,  and  the  dead  elements 
with  a  great  number  of  microbes  are  thus  expelled.  Nevertheless, 
virulent  agents  remain  in  the  focus,  and  it  ma}^  be  asked  how  a  cure 
is  ever  possible,  especially  when  the  purulent  focus  becomes  encysted. 
In  such  cases,  the  author  believes  a  chemical  modification  of  the 
fluids  and  tissues  of  the  organism  takes  place,  rendering  the  media 


SUPPURATION.  i\\ 

unfavorable  for  the  developmenl  of  the  microbe  .  The  vitality  of 
the  latter  gradually  declines,  and  their  removal  by  phagocyte  i 
easily  accomplished.  II'  the  focu  remains  closed,  cure  i  po  3ible, 
but  the  pus  then  undergoes  tran  formation  .  [n  some  instances  the 
elements  of  which  it  is  composed  undergo  fal  ty  degeneration,  -<<  thai 
the  focus  is  transformed  into  a  chyliform  fluid.  In  other  cases,  the 
scrum  is  absorbed  and  I  here  remain  a  ca  eou  mass  which  may  later 
become  infiltrated  with  calcareous  suits. 

The  suppurative  process  is  attended  by  local  and  general  symp- 
toms. The  local  symptoms  are  well  known  as  the  four  cardinal  signs 
of  inllaniniaiion— swelling,  pain,  heat,  and  redness  (tumor,  dolor, 
color  et  ruber).  The  primary  phenomenon  is  tumefaction,  due  to 
nutritive  and  vascular  modifications  which  attend  and  explain  the 
pyogenesis. 

Pain,  which  is  often  the  first  appreciable  phenomenon,  is  due  to 
increased  sensitiveness  of  the  parts  by  the  excessive  influx  of  blood; 
to  irritation  or  rupture  of  nerve  filaments,  and,  finally,  to  compres- 
sion of  neighboring  parts. 

Heat  and  redness  are  two  symptoms  which  have  been  described 
according  to  the  evolution  of  superficial  suppurations  and  which  are 
attributed  to  an  exaggerated  afflux  of  blood,  augmentation  of  nutri- 
tive exchange,  and  proliferation  of  cells.  No  experiments,  however, 
have  as  yet  been  made  to  verify  whether  suppuration  in  deep-seared 
organs  is  also  attended  with  a  local  rise  of  temperature. 

When  undisturbed,  an  abscess  tends  to  open  either  into  a  neigh- 
boring organ  or  outwardly.  When  opened,  whether  naturally  or  sur- 
gically, the  pus  and  the  pyogenic  microbes  pass  out  of  the  focus,  and 
this  is  folloAved  by  alleviation  of  the  local  and  general  symptoms. 
In  some  cases  evacuation  is  accomplished  at  once,  and  cicatrization 
is  soon  established.  More  often,  however,  the  pus  re-forms  and  the 
process  lasts  for  a  more  or  less  prolonged  period. 

The  local  manifestations  are  in  most  cases  accompanied  by  general 
phenomena.     When  the  latter  appear  in  the  beginning  of  the  pre-    -  - 
a  grave  infection  is  to  be  feared,  since  they  indicate  a  special  viru- 
lence of  the  pathogenic  agent. 

We  do  not  need  to  dwell  here  upon  the  various  disturbances  which 
may  be  observed.  They  are  those  common  to  all  infectious  pro- 
cesses. The  onset  is  characterized  by  chills :  a  rise  of  temperature 
then  occurs:  the  fever  may  be  continuous  or  remittent,  or  even 
frankly  intermittent.     At  a  more  advanced  stage  it  may  assume  a 


212  IXFECTIO  US  DISEASES. 

hectic  character,  accompanied  by  secretory  modifications,  albumin- 
uria, etc.,  which  will  be  referred  to  again. 

Cold  Suppurations.  From  the  point  of  view  of  their  evolution, 
abscesses  have  been  divided  into  two  classes:  hot  abscesses,  with  an 
acute  and  clearly  inflammatory  evolution,  and  cold  abscesses,  char- 
acterized by  a  slow  and  indolent  progress.  The  latter  are  often  due 
to  the  tubercle  bacillus.  It  was  at  one  time  assumed  that  they  were 
always  dependent  upon  the  pathogenic  agent  named.  Recent  con- 
tributions demonstrate,  however,  that  cold  abscesses,  whether  cuta- 
neous or  osseous,  are  not  necessarily  of  tuberculous  nature.  The 
author  observed  a  case  of  cutaneous  cold  abscess  clue  to  a  common 
pus  coccus,  the  staphylococcus  aureus.1  Facts  of  this  kind  are  not 
rare.  Hallopeau2  has  reported  two  interesting  cases,  and  Hulot,3  in 
an  interesting  thesis,  has  described  cutaneous  suppurations  which 
evolve  like  tubercular  lesions  and  are  attended  by  a  progressive 
cachexia  ending  in  death.  These  cold  streptococcic  abscesses  are 
especially  frequent  in  children,  although  they  may  also  be  observed 
in  adults.  A  similar  evolution  may  also  be  observed  in  cases  of 
osteomyelitis. 

In  most  instances,  however,  cold  suppurations  of  the  bones  are  clue 
to  Eberth's  bacillus.  We  find  in  the  memoire  of  Chantemesse  and 
Widal  a  great  number  of  observations  proving  the  slow  and  insidious 
course  of  certain  osteomyelites  of  typhoid  origin. 

Suppuration  in  the  Various  Parts  of  the  Organism. 

All  parts  of  the  organism  are  not  equally  liable  to  invasion  by 
pyogenic  microbes.  Suppuration  is  rare  in  cartilages,  owing,  perhaps, 
to  their  scanty  vascularization.  There  are,  however,  inexplicable 
differences  between  analogous  tissues.  Thus,  while  abscesses  are 
quite  frequent  in  the  brain,  the  spinal  cord  is  very  seldom,  if  ever, 
the  seat  of  a  purulent  focus.  The  same  is  true  with  reference  to 
muscular  tissue.  There  are  but  three  muscles  which  are  at  times 
invaded  by  suppuration,  namely,  the  iliac  psoas,  the  sternocleido- 
mastoid, and  the  deltoid.  The  resistance  of  the  lungs  is  also  very 
remarkable.  In  spite  of  the  frequency  of  infections  and  the  great 
number  of  pyogenic  germs  entering  the  respiratory  tract,  pulmonary 

1  Roger.  Abces  froids  dus  au  staphylocoque  dore.  Gazette  hebdomadaire,  August 
6,  1892. 

2  Hallopeau.  Abces  cutanes  et  sous-cutanes  multiples  et  recidivants  chez  les  jeunes 
enfants.     Annales  de  dermatologie,  1894. 

3  Hulot.     Infection  d'origine  cutanee  chez  les  enfants.     These  de  Paris,  1895. 


SUPPURATION.  213 

suppurations  are  quite  limited  and  special.     No  more  than  small 
purulent  points  are  observed  in  bronchopneumonia  foci;  the  pr< 
is  suppuration  in  the  cavities.    True  pulmonary  absce     i    ol 
rare  occurrence. 

Whatever  the  suppurating  organ  or  tissue  under  observation  may 
be,  the  same  pyogenic  agents  are  always  discovered.  Aside  from  the 
specific  suppurations,  the  microbes  Pound  in  pus  are  generally  the 
staphylococcus  or  the  streptococcus,  the  colon  bacillus,  the  pneumo- 
coccus,  and  less  frequently  the  tel  ragenus  or  various  species  of  minor 
importance.  It  is  to  be  remembered,  however,  thai  the  rel 
frequency  with  which  these  pyogenic  species  are  mel  with  varies 
considerably  according  to  the  part  affected,  ft  is  readily  cona 
thai  the  bacteriological  nature  of  a  suppuration  oiusl  be  related  to 
the  species  normally  inhabiting  the  region  invaded. 

Cutaneous  Suppurations.    The  researches  of  Remlinger  shovi  thai 
there  are  40,215  bacteria  to  the  square  centimetre  of  skin.     I 
eight  out  of  fifty  colonics  are  composed  of  staphylococci.    C 
quently,  when  a  suppuration  occurs  in  the  skim  this  microbe  will  be 
found  in  most  cases. 

Buccopharyngeal  Suppurations,  ft  is  not  the  staphylococcus  but 
the  streptococcus  that  is  most  frequently  met  with  in  buccopharyn- 
geal suppurations,  since  the  latter  microbe  is  constantly  present  in 
the  mouth.  Some  other  pyogenic  species,  such  as  the  tetragenus, 
pnemnococcus,  staphylococcus,  proteus  vulgaris,  and  colon  bacillus 
are  also  found,  but  in  small  numbers.  It  is  the  streptococcus  which 
easily  becomes  exalted  and  gives  rise  to  the  different  varieties  of 
phlegmonous  sore  throat  and  abscesses  of  the  tonsils. 

Nasal  Suppurations.  It  is  admitted  that  the  staphylococcus  is 
the  microbe  concerned  in  most  cases  of  purulent  rhinitis.  There  is 
no  doubt  that  this  coccus  does  produce  nasal  suppurations.  The 
author  has  found  it  in  abscesses  of  the  septum  in  a  state  of  purity. 
It  is  well  to  remark  that  the  mucopus  flowing  from  the  nares  before 
the  abscess  was  opened  contained  no  microbes  other  than  the  staphy- 
lococcus. 

It  is  important  to  call  attention  to  the  frequency  and  gravity  of 
purulent  coryza  of  streptococcic  origin  in  scarlatina.1  It  is  an  early 
manifestation  characterized  by  a  continuous  discharge  and  often 
accompanied  with  enormous  cervical  adenopathies  and  suppurative 

1  Chausserie-Lapree.    De  la  rhinite  purulente  clans  la  scarlatine     These  de  Paris.  1900. 


214  IXFECTIO  US  DISEASES. 

otitis.  The  microscopic  examination  reveals  the  streptococcus 
almost  in  a  state  of  purity.  The  streptococcus  was  found  associated 
with  the  staphylococcus  aureus  in  one  case.  This  impure  culture 
inoculated  into  a  guinea-pig  caused  death  of  this  animal  in  forty- 
eight  hours. 

Auricular  and  Ocular  Suppurations.  Otitis  media  may  be  due  to 
anaerobic  microbes,  but  in  most  cases  it  depends  upon  the  strepto- 
coccus, pneumococcus,  staphylococcus,  tetragenus,  the  bacillus  of 
Friedlaender,  and  the  bacillus  proteus.  The  pneumococcus  is  par- 
ticularly frequent  in  primary  otites,  the  streptococcus  in  secondary. 
All  may  give  rise  to  lesions  in  more  or  less  distant  parts,  especially 
to  suppuration  of  the  mastoid  cells,  phlebitis  of  the  sinuses,  abscess 
of  the  cerebrum  and  cerebellum,  meningites,  and  even  pyemia. 
When,  however,  suppuration  has  lasted  for  some  time,  the  microbe 
or  microbes  which  may  have  been  present  in  the  beginning  of  the 
process  disappear  and  the  staphylococcus  alone  is  found.  Such  at 
least  is  the  fact  in  odorless  suppurations,  since  pus  which  becomes 
fetid  contains  anaerobic  organisms  capable  of  invading  the  mastoid 
and  giving  rise  to  gangrenous  septicemia  and  to  suppurative  foci  in 
distant  parts. 

Unlike  the  suppurations  of  the  parts  already  mentioned,  those  of 
the  eye  seem  to  be  due,  in  most  cases,  to  specific  microbes.  Puru- 
lent conjunctivitis  generally  depends  upon  the  gonococcus.  Other 
microbes,  however,  may  likewise  be  concerned,  such  as  the  bacillus 
of  Koch-Weeks  and  the  ordinary  pyogenics. 

Suppurations  of  the  Respiratory  Passages.  In  the  deep  parts  of 
the  respiratory  passages  the  ordinary  pyogenic  microbe  is  the  pneu- 
mococcus, as,  for  instance,  in  cases  of  bronchopneumonia,  in  which 
the  streptococcus,  the  pneumobacillus,  and  the  staphylococcus  may 
also  be  found,  but  less  frequently. 

In  cases  of  fibrinous  pneumonia  suppuration  is  exceptional.  When 
it  occurs  it  is  due  to  a  secondary  infection  with  the  staphylococcus 
aureus,  seldom  with  the  streptococcus  or  pneumobacillus.  Contrary 
to  classical  opinion,  however,  it  seems  to  be  established  that  the 
suppuration  of  a  pneumonic  focus  may  be  due  to  the  pneumococcus 
alone.  This  is  clearly  evidenced  by  the  observations  of  Zenker  and 
especially  by  the  researches  of  Griffon,  who  studied  five  cases  of 
suppurative  pneumonia. 

Suppurations  of  the  Digestive  Canal.  The  colon  bacillus  and  the 
intestinal  streptococcus  were  until  recently  held  to  be  chiefly  respon- 


SUPPURATION.  216 

sible  for  suppurations  of  the  alimentary  canal.    The  anaerobic 
cies,  and  notably  B.  ramosus  of  Veillon,  are  al  presenl  suppo  '-'I  to 
play  a  more  important   role    Concerning  this  subject   we  po 
very  few  documents.     All  we  know   with  regard  to  phlegmonous 
enteritis  is  contained  in  the  work  of  Ziegler  and  Mint/,  who  detected 
the  streptococcus.    The  production  of  hemorrhoidal  phlebitee  and 
anal  abscesses  is  attributed  to  the  colon  bacillus.     We  are  better 
in  torn  km  I  as  regards  appendicitis.   Mosl  authorities  admil  the  action 
of  the  colon  bacillus  and  streptococcus.    Veillon  argues   thai  the 
principal  role  is  played  by  the  B.  ramoms,  and  he  think-  thai  the 
fetid  character  of  the  pus  and  the  gangrenous  state  of  the  wall-  pi 
the  anaerobic  nature  of  the  process.     Appendicitis  is,  therefore,  held 
by  many  to  be  a  variety  of  enteritis,  its  particular  character  being 
due  simply  to  the  special  anatomical  conditions  of  the  affected  part. 

Experimental  Appendicitis.  In  order  to  elucidate  the  mechanism 
of  appendicitis  experimentation  was  resorted  to  by  Roux  (of  Lau- 
sanne). As,  however,  he  operated  upon  the  pig — an  animal  without 
an  appendix — he  previously  created  an  appendix  at  the  expens 
the  cecum,  and  obtained  negative  results.  Taking  up  the  question 
with  Dr.  Josue,1  we  operated  upon  the  rabbit.  The  appendix  of  this 
animal  differs  from  that  in  man  in  that  it  is  far  more  voluminous 
and  is  in  free  communication  with  the  cecum,  but  its  analog}'  with 
the  appendix  of  man  is  admitted  by  anatomists,  such  as  Krause, 
Ribbert,  etc. 

Some  time  after  the  publication  of  our  researches  on  experimental 
appendicitis  the  question  was  taken  up  by  Dr.  Gervais,  who  con- 
firmed our  conclusions,  and  by  Beaussenat,  who  obtained  appendi- 
cites  by  exciting  gastrointestinal  disturbances.  Dr.  Chastanet2  pur- 
sued experimental  researches  in  our  laboratory  and  demonstrated 
that  it  is  possible  to  induce  appendicitis  in  the  rabbit  by  causing 
this  animal  to  swallow  microbic  cultures.  The  appendix  becomes 
affected  the  same  as  the  other  portions  of  the  digestive  canal,  but 
its  reparation  seems  to  be  less  easy.  Chastanet  further  determined 
this  difference  by  producing  traumatism  in  the  various  portions  of 
the  intestine  and  noticing  that  the  lesions  of  the  appendix  persisted 
long  after  cicatrization  of  the  lesions  in  the  other  parts.  The  lesions 
found  in  all  these  experiments  were  ulcers.     These  facts  lead  to  the 

1  Roger  et  Josue.    Appendieite  experimentale.     Society  med.  des  hopitaux,  Jan.  31. 
1S96.     Recherches  experimentales  sur  I'appendicite.     Revue  de  inedecine.  June.  1  - 

2  Chastanet.     Recherches  experimentales  sur  I'appendicite.     These  de  Pari-.  1897 


216 


INFECTIOUS  DISEASES. 


conclusion  that  the  appendix  represents  a  lymphoid  organ,  compar- 
able to  the  tonsil.  Like  the  latter,  it  is  frequently  the  seat  of  acute 
primary  or  secondary  infections.  This  is  what  happens  when  the 
intestinal  germs  become  exalted  in  consequence  of  some  dietetic 
error,  a  depressing  cause,  or  an  infectious  or  other  disease.  The 
appendicular  inflammation  may  be  slight  and  be  completely  repaired. 
In  other  cases  it  is  expressed  by  ulcerations,  which  are  less  easily 

Fig.  2. 


Experimental  appendicitis  of  eighteen  days'  standing. 


reparable.  The  latter  may  cicatrize  or,  on  the  contrary,  give  rise  to 
adhesions  which  constrict  the  cavity  and  often  obliterate  it.  Primary 
obliteration  of  the  appendix  is  hardly  conceivable.  The  idea  that 
its  obliteration  represents  the  last  stage  of  an  ulcerating  process 
seems  to  be  in  perfect  harmony  with  the  ensemble  of  published  facts. 
In  our  own  experiments  it  was  found  necessary  to  inject  virulent 
microbes  into  the  intestinal  cavity  in  order  to  induce  appendicitis. 


SUPPURATION. 


217 


Aseptic  ligation  of  the  appendix  Is  sufficient.    The  rabbit*   thus 
operated  upon  first  lose  flesh  and  seem  to  be  Buffering.    They 
recover,  however,  grow  fat,  and  qo  longer  presenl  any  disturbance. 
Nevertheless,  at  the   end  of  a  few  days,  palpation  of  the  abdomen 
reveals  the  presence  of  a  deep-seated   tumor,  of 
greater  or  less  size  and   consistency,  situated  to 
(lie  right  side  of  the  median  line.    The  majority  of 
the  animals  thus  survive  almost  indefinitely.  They 
had  to  bo  killed  in  order  to  study  the  course  of  the 
lesions.    Some  rabbits  died  a  few  days  after  the 
((Iteration.    Those  suffered  from  a  profuse  diarrhea, 
and  rapidly  emaciated. 

The  lesions  vary,  of  course,  according  to  the 
length  of  time  since  the  operation.  The  day  fol- 
lowing the  operation  the  walls  of  the  appendix 
are  found  to  be  more  vascularized  than  normally; 
its  cavity  is  distended  by  a  variable  quantity  of 
serosity.  The  second  day  the  surface  of  the  cavity 
is  covered  with  a  purulent  layer.  From  the  fourth, 
at  times  even  from  the  third  day  onward,  soft  but 
highly  vascularized  adhesions  are  formed.  The 
color  of  the  appendix  is  milk-white,  suggestive 
of  a  purulent  transformation.  The  cavity  con- 
tains a  greenish  substance.  On  the  sixth  day  the  appendix  still 
presents  an  almost  normal  aspect,  but  it  is  closely  adherent  to  the 
surrounding  intestinal  coils.  Its  contents  are  mixed  with  pus  and 
some  purulent  floating  flocculi. 

The  entire  inside  of  the  appendix  then  undergoes  a  purulent  trans- 
formation. Coincident ly,  the  walls  become  distended,  so  that  toward 
the  eighth  clay  an  ovoid  cyst  is  found  measuring  about  3  cm.  in 
diameter.  (Fig.  2.)  After  having  reached  this  degree  of  develop- 
ment, the  purulent  pouch  seems  to  remain  stationary,  as  we  were 
able  to  convince  ourselves  by  killing  one  of  the  animals  three  months 
after  ligation  of  the  appendix.  (Fig.  3.) 

In  no  case  did  we  observe  the  pouch  open  into  the  peritoneum, 
but  in  several  it  was  so  thin  at  certain  points  that  rupture  might 
well  occur  sooner  or  later. 

The  microscopic  examination  of  the  pus  reveals  the  presence  of 
leucocytes  and  microbes.  In  old  cases,  the  leucocytes  undergo 
granulofatty  degeneration.      Bacilli  are  rare.     In  some  cases  it  is 


Experimental  ap- 
pendicitis "f  three 

months'  standing. 


218  INFECTIO  US  DISEASES. 

necessary  to  resort  to  cultures  to  demonstrate  the  presence  of  the 
colon  bacillus. 

Histological  examination  reveals  extensive  lesions.  Fig.  4  rep- 
resents the  state  of  the  walls  three  days  after  the  operation.  When 
slightly  magnified,  it  is  seen  that  the  general  structure  of  the  appen- 
dix is  preser\  ed. 

Fig.  4. 
v.'C      h  '  N)  ••>'-'•  •'•'.'  '"    •'.'■  >"> 


•  ■:. 


Wall  of  the  appendix  at  the  third  day  after  ligation.    X  8  diameters. 

If  a  more  advanced  case  is  examined,  for  instance,  one  fifteen  days 
old,  it  is  seen  that  the  normal  structure  of  the  organ  has  completely 
disappeared.  (Fig.  5.)  When  slightly  magnified  it  appears  like  a 
compact  tissue  with  irregular  contour,  presenting  here  and  there  foci 
of  necrosis. 

Fig.  5. 

r  — -a  5'7    '   r'~ 


iPwv,,.. 


''  "*" 

Wall  of  the  appendix  fifteen  days  after  ligation.    X  6  diameters. 

With  high  magnification  is  seen  a  fibrillary  tissue  with  numerous 
nuclei.  At  certain  points  there  are  some  foci  of  necrosis  vaguely 
recalling  the  form  of  follicles.  Elsewhere  are  found  embryonic 
masses  made  up  of  infectious  nodules.  The  presence  of  a  few  mus- 
cular cells  may  yet  be  perceived.  It  is  impossible  to  detect  microbes 
in  the  sections. 


SUPPURATION.  219 

The  importance  recently  attributed  to  foreign  bodies  in  the  appen- 
dix led  us  to  make  another  series  of  experiments.  We  introduced 
into  the  appendix  of  two  rabbits  a  ball  of  wax,  of  sufficienl  size  in 
one  of  the  cases  to  distend  the  intestinal  walls.  No  disturbance 
resulted  from  the  operation.  The  animals  were  killed  at  the  end  of 
a  fortnight  and  no  lesions  were  found.  The  appendix  . 
lutely  normal.  Moreover,  the  foreign  body  could  nol  be  found,  as, 
in  spile  of  its  considerable  Bize,  h  had  been  forced  oul  by  the  con- 
tractions of  the  appendix. 

Prom  our  scries  of  experiments  ii  is  seen  thai  only  one  experi- 
mental procedure  produces  ulcerative  appendicitis,  viz..  complete 
ligation  of  the  appendix.  The  cul-de-sac  musl  be  transformed  into 
a  closed  cavity.  Even  double  si  rid  ure  does  not  cause  inflammation, 
nor  does  the  introduction  of  a  ball  of  wax. 

It  now  remains  to  account  for  the  manner  in  which  the  suppuration 
of  the  appendix  is  produced  when  completely  ligated.  It  is  not  the 
result  of  an  arrest  of  the  circulation,  since  the  numerous  vessels 
passing  through  the  peritoneal  fold  amply  suffice  to  insure  the  circu- 
lation. In  fact,  if,  after  having  ligated  the  appendix,  an  appen- 
dicular fistula  be  created,  by  which  the  free  extremity  of  the  0 
is  connected  with  the  exterior,  no  notable  incident  occurs.  As  s< 
however,  as  the  fistula  is  obliterated  and  the  cul-de-sac  is  I  ransfi  >] 
into  a  closed  cavity,  suppuration  sets  in.  This  simple  experiment 
demonstrates  that  suppuration  is  produced  because  an  arrest  of  the 
flow  of  fluids  occurs.  ^Ye  resorted  to  another  series  of  experiments 
"which  proved  that  the  suppuration  is  not  due.  as  some  authori- 
ties suppose,  to  exaltation  of  pyogenic  germs.  Cultures  made  with 
a  few  drops  of  the  contents  of  a  normal  appendix  proved  capabl 
producing  suppurative  lesions  in  rabbits  and  death  in  nine  day-. 
while  similar  cultures  prepared  two  or  three  days  after  ligation  of 
the  appendix  had  exactly  the  same  virulence  as  those  made  before 
the  operation.  After  the  fourth  day  the  pathogenic  power  of  the 
intestinal  contents  declined  rapidly.  It  is  a  general  law,  that  in 
purulent  foci  microbes  become  progressively  weaker,  and  even  finally 
disappear.  The  mechanism  of  appendicular  suppuration  is  the  same 
as  that  governing  the  formation  of  all  purulent  foci.  In  fact,  it  is 
known  that  pyogenic  microbes  act  by  virtue  of  the  soluble  sub- 
stances which  they  secrete.  Under  normal  conditions,  however,  the 
products  of  the  microbes  in  the  appendix  are  discharged  with 
the  fecal  matters.     After  ligation  the  toxins  accumulate  and.  as  the 


220  INFECTIOUS  DISEASES. 

experiments  of  Poliakoff  have  shown,  the  products  of  the  pyogenic 
germs  act  particularly  when  they  are  elaborated  slowly  and  progres- 
sive^. We  are  thus  led  to  the  conclusion  that  appendicitis  depends 
upon  the  general  causes  of  suppuration.     It  is  a  tox-infectious  lesion. 

Abscesses  of  the  Liver.  The  portal  vein  represents  the  main 
channel  for  the  introduction  of  microbes  into  the  liver.  As  hepatic 
abscesses  are  connected  with  intestinal  lesions,  it  is  the  portal  vein 
which,  owing  to  its  anatomical  connections,  insures  morbid  sym- 
pathy between  the  alimentary  canal  and  the  liver.  In  some  cases 
germs  pass  through  this  vessel  without  leaving  any  trace,  as  is  notably 
the  case  in  dysentery.  In  other  instances  a  suppurative  pylephle- 
bitis affecting  the  entire  portal  system  and  its  contributory  branches 
occurs  and  represents  an  intermediate  incident  accounting  for  the 
propagation. 

After  dj^sentery,  we  must  also  cite,  among  intestinal  affections 
which  give  rise  to  hepatic  suppurations,  all  those  which  are  respon- 
sible for  intestinal  ulcerations:  typhoid  fever,  tuberculous  enteritis, 
tyj  ihlitis,  and  appendicitis.  It  is  to  be  noted,  however,  that  abscesses 
are  as  rare  under  these  conditions  as  they  are  frequent  in  dysentery. 

The  most  varied  pyogenic  microbes  may  be  encountered  in  hepatic 
suppurations.  The  streptococcus  as  well  as  the  colon  bacillus  and 
the  staphylococcus  are  found.  Dr.  Lannois  has  reported  an  inter- 
esting observation  of  an  hepatic  abscess  with  Eberth's  bacillus 
occurring  in  the  course  of  a  typhoid  fever  and  caused  by  a  pyle- 
phlebitis. 

A  point  of  interest  in  the  history  of  hepatic  abscesses  is  the  fact 
that  the  pus  is  often  sterile.  This  has  been  clearly  ascertained  in 
forty  observations.  As  has  already  been  remarked,  every  old  sup- 
purative focus  finally  becomes  sterile,  but  some  hepatic  abscesses, 
by  no  means  old,  have  been  found  equally  free  from  microbes.  The 
explanation  is  found  in  the  well-known  destructive  action  of  the  liver 
upon  bacteria. 

Dysenteric  abscesses  of  the  liver  are  seldom  sterile.  Out  of  thir- 
teen cultures  made  by  Kartulis,  microbes  developed  in  five  instances. 
The  staphylococci  aureus  and  albus,  and  the  B.  proteus  vulgaris 
were  the  species  found  under  these  conditions.  On  the  other 
hand,  examination  of  sections  demonstrated  that  the  walls  of  the 
abscesses  contained  bacteria,  even  when  the  cultures  were  negative. 
Such  was  the  result  in  ten  cases.  There  remain,  therefore,  but  three 
observations  of  sterile  abscesses. 


SUPPURATION.  221 

Whether  bacteria  are  detected  or  aot,  Kartulis  always  found 
amebaD.  Some  experimenl  pursued  by  Marchoux  upon  cat*  show 
that  dysenteric  abscesses  of  the  liver  ma)  re  all  from  the  injection 
of  dysenteric  stools  containing  amebse. 

Suppurations  of  the  Pancreas.  Although  placed  anatomically  in 
a  sufficiently  analogous  situation,  the  pancrea  i  far  less  frequently 
affected  than  the  liver.  Like  the  latter  organ,  it  is  infected  either 
by  germs  carried  to  it  by  the  bloodvessels  or  by  bacteria  entering 
it  by  way  of  the  excretory  channels.  The  conditions  favoring  infec- 
tion are  evidently  the  same  in  both  in  tances.  Pancreatic  suppu- 
rations may,  then,  be  observed  in  puruleul  infections,  in  variola, 
appendicitis  and  in  consequence  of  lesion  of  the  stomach  and  duo- 
denum. The  colon  bacillus  is  the  microbe  found  in  the  majority 
of  cases,  and  it  seems  thai  the  localization  of  this  microbe  i- 
favored  by  the  previous  lesions  of  the  organs — cyst.-,  sclerosis, 
lithiasis. 

Suppurations  of  the  Urinary  and  Genital  Organs.  Like  the  diges- 
tive apparatus,  the  genito-urinary  tract  communicates  by  its  ter- 
minal end  with  the  external  world.  It  may,  therefore,  be  infected 
from  without  as  well  as  from  within.  In  man,  however,  protection 
against  the  outward  germs  is  fairly  well  insured.  Under  normal 
conditions,  microbes  do  not  penetrate  beyond  the  fossa  navicularis. 
Nevertheless,  bacteria  are  not  infrequently  found  in  the  urethra  of 
men  otherwise  healthy,  notably  the  streptococcus  giganteus  urethras. 
The  bladder  offers  great  resistance  to  microbic  invasion.  It  is  quite 
difficult  to  infect  it  when  healthy.  This  is  no  longer  true,  however, 
when  it  is  the  seat  of  a  lesion  or  when  some  obstacle  opposes  the 
free  discharge  of  the  urine.  Upon  a  soil  thus  prepared  the  most 
varied  pathogenic  agents  develop  abundantly,  inducing  suppuration 
of  the  bladder,  ureters,  pelvis,  and  kidneys.  They  may  even  go 
farther  and  give  rise  to  perinephritic  phlegmons. 

The  gonococcus,  which  is  to-day  held  to  possess  greater  migratory 
powers  than  was  formerly  believed,  represents  in  women  an  impor- 
tant cause  of  salpingitis.  According  to  the  researches  of  E.  Reymond, 
it  vegetates  upon  the  surface  of  the  mucous  membrane  in  the  desqua- 
mated epithelial  cells  and  but  exceptionally  invades  the  walls  of  the 
Fallopian  tubes.  In  streptococcic  salpingitis,  on  the  contrary,  the 
microbe  strongly  tends  to  propagate  toward  the  peritoneum.  Finally. 
the  salpingites  due  to  the  colon  bacillus  are  observed  in  those  c  -  - 
in  which  adhesions  are  formed  between  the  intestine  and  the  Fallo- 


222  ISEECTIOUS  DISEASES. 

pian  tubes.     This  fact  leads  to  the  opinion  that  the  colon  bacillus 
is  derived  from  the  intestine. 

Suppurations  of  the  Nerve  Centres.  The  other  parts  of  the  organ- 
ism not  communicating  with  the  exterior  cannot  be  attacked  by 
pyogenic  microbes,  except  as  a  result  of  traumatism,  which  allows 
them  in  penetrate  directly,  or  of  extension  of  a  neighboring  lesion, 
or  of  a  general  infection  ending  in  localizations.  The  relative  fre- 
quency of  the  microbic  species  found  under  these  conditions  will  at 
times  depend  upon  the  situation  of  the  part  affected.  Abscesses  of 
the  cerebrum  and  cerebellum  being  in  most  cases  consecutive  to 
otitis,  the  microbes  found  are  those  concerned  in  suppurations  of  the 
middle  ear. 

Suppurations  of  the  Serous  Membranes.  Serous  membranes  are 
generally  invaded  by  contiguity,  as  a  result  of  a  purulent  focus  devel- 
oping in  subjacent  organs.  Such,  however,  is  not  always  the  case. 
Localization  may  first  occur  in  the  nervous  system,  as  is  the  case 
with  articulations.  The  same  is  true  with  regard  to  the  meninges, 
pleura,  and  peritoneum. 

In  the  pleurisy  of  children  the  pneumococcus  is  the  microbe  com- 
monly found.  The  streptococcus  is  comparatively  seldom  met  with. 
In  adults,  on  the  contrary,  the  streptococcus  is  more  frequently 
found  than  the  pneumococcus.  Among  the  other  pyogenic  microbes, 
we  mrdy  cite  the  staphylococcus,  the  bacillus  of  Friedlaender,  the 
typhoid  bacillus,  and  the  colon  bacillus.  These  findings  are  not 
merely  of  theoretical  interest.  It  is  known  that  recovery  from  puru- 
lent pleurisy  is  very  frequent  in  cases  in  which  the  pneumococcus  is 
the  pathogenic  agent.  The  differential  diagnosis  may  be  at  least 
suspected,  if  not  established,  by  simply  taking  into  account  the 
course  of  events  and  especially  the  characters  of  the  fluid.  In  the 
majority  of  cases  the  pus  of  pneumococcic  pleurisies  is  thick,  viscous, 
and  greenish.  That  of  streptococcic  pleurisies  contains  a  greater 
proportion  of  serum  and  gives  a  grayish  deposit.  Certainty  is,  of 
course,  to  be  reached  only  by  bacteriological  research.  In  this  con- 
nection it  may  be  stated  that  a  purulent  pleurisy,  the  fluid  of  which 
is  free  from  bacteria,  must  be  considered  tuberculous  in  nature 
(Fraenkel). 

The  principal  cause  of  peritonitis  being  in  the  intestines,  it  is 
readily  conceived  that  peritonitis  due  to  the  colon  bacillus  must  be 
quite  frequent.  The  intervention  of  the  colon  bacillus  also  accounts 
for  typhoidal  peritonites.     This  is  not  invariably  the  case,  however. 


SUPPURATION.  223 

Fraenkel  has  reported  a  case  in  which  the  exudate  ol  a  peritonitis 
occurring  in  the  course  of  a  typhoid  fever  contained  no  other  microbe 
than  the  typhoid  bacillus.  When  infection  of  the  peritoneum  occurs 
through  the  genital  organs,  as  is  the  ca  e  e  pecially  in  women,  the 
gonococcus  is  sometimes  found,  bu1  tnore  frequently  the  strepto- 
coccus. 

In  most  cases  of  purulenl  pericarditis  the  inflammation  depends 
upon  a  genera]  infection,  bul  it  may  occur  independently  or  accom- 
pany oilier  purulent  lesions  affecting  the  viscera  or  serous  mem- 
branes. That  is  to  say,  purulenl  pericarditis  is  seldom  primary.  I' 
represents  the  localization  of  an  infect  ion  the  starting  point  of  which 
escaped  observation.  Suppurative  pericarditis  sometimes  occui 
a  result  of  affection  of  the  respiratory  apparatus — i.  c,  pneumonia, 
bronchopneumonia,  even  dilatation  of  the  bronchi,  and,  in  these 
instances,  it  is  due  to  the  pneuinococcus.  It  is  sometimes  consecu- 
tive to  an  eruptive  fever:  measles,  varicella,  and.  above  all,  scarla- 
tina and  smallpox.  It  is,  however,  a  complication  of  far  rarer  occur- 
rence than  was  formerly  believed.  My  own  statistics,  inclui  ling  531 1 1 
cases  of  eruptive  fevers,  show  but  two  cases  of  purulent  p<  ricarditis. 

The  pneuinococcus  and  streptococcus  are  the  two  microbes  mosi 
frequently  concerned  in  purulent  meningitis.  Among  the  bacteria 
of  uncommon  occurrence  we  may  cite  the  staphylococcus  aureus,  the 
typhoid  and  colon  bacilli,  and  the  bacillus  of  influenza.  AVe  do  not 
include  the  lneningites  of  specific  nature,  caused  by  Koch's  bacillus, 
and  the  epidemic  cerebrospinal  meningitis  which  depends  upon  a 
particular  microbe — the  meningococcus  of  "Weichselbaum  (diplococ- 
cus  intracellularis),  formerly  confounded  with  the  pneuinococcus. 

Meningitis  is  not  frequent  in  eruptive  fevers.  I  have  met  with 
but  one  case.  An  otitis,  developing  in  a  man  convalescing  from 
measles,  became  the  starting  point  of  a  purulent  infection.  Numer- 
ous suppurative  foci  appeared  in  the  joints,  and  at  the  necropsy 
the  meninges  were  found  full  of  pus.  This  lesion,  in  spite  of  its 
intensity,  had  remained  absolutely  latent.  The  patient  had  retained 
consciousness  to  the  last,  and  never  complained  of  any  suffering  in 
the  head.  The  absence  of  morbid  manifestations  is  probably  to  be 
attributed  to  the  absence  of  dropsy  of  the  ventricles.  The  author 
would  like  to  remark  that,  at  all  events,  suppurative  meningites. 
even  when  extensive,  occur  in  a  latent  manner  oftener  than  is 
believed.     They  are  expressed  by  no  symptoms  whatever. 

If  wTe  consider  the  ensemble  of  the  results  to  which  the  study  of 


994  INFECTIOUS  DISEASES. 

suppuration  leads  us,  Ave  perceive  that  pus  originates  when  the 
leucocytes  fail  in  their  task  of  destruction  of  the  invading  microbes. 
Numbers  of  cells  are  killed  by  microbic  secretions.  Their  cadavers 
constitute  the  pyocytes — useless  cells,  true  foreign  bodies — which 
must  be  eliminated.  If  these  are  not  very  numerous,  the  macro- 
phages remove  them.  In  most  cases,  discharge  occurs  outwardly 
and  suppuration  becomes  established.  Suppuration,  then,  is  the 
establishment  of  an  exit  for  the  microbes,  toxins,  and  destroyed  cells. 
Suppuration  is  a  common  process  to  which  a  great  number  of  para- 
sites may  give  rise.  But  all  of  them  act  in  the  same  way,  viz.,  by 
secreting  necrotizing  substances.  Suppuration  is  reaction  against 
toxins.  In  order  for  this  reaction  to  be  produced,  the  organism  must 
possess  a  certain  degree  of  resisting  power.  If  it  is  incapable  of 
reacting,  two  events  are  possible:  first,  reaction  being  insufficient 
or  nil,  the  pyogenic  micro-organisms  invade  the  whole  organism;  they 
cease  to  produce  pus,  and  give  rise  to  septicemia.  Second,  the  necro- 
tizing action  of  the  toxins  is  so  strong  that  the  tissue  cells  undergo 
fermentations  analogous  to  those  which  characterize  putrefaction. 
AVe  then  find  ourselves  confronted  by  a  new  process — another  ter- 
mination of  inflammation — related  to  suppuration  by  numerous 
transitions.  It  is  this  process  that  we  are  now  about  to  study, 
namely,  gangrene. 


(Ml  A  PTEE    VIII. 

GANGRENE. 

Definition  of  Gangrene.    Onu  ch  Kavoring  the  Developmenl  "\  Gangrene,    [mportanoe 
of  Vascular  and   Nervous  Lesions.     Auxiliary  Rdle  •>(  Certain  Toxic   £ 
Study  of  the  Principal  Agents  of  Gangrene.     Rdle  of    \iia§robic  Microbes.     Ii«'«l<- 
of  Facultative  Anaerobics.     The  Agents  of  Gangrenous  Uammitia<     The  Microbe 

of  I'.rnign  Gangrene  of  the  Kvelid  .  i:.,i.-  of  Pyogenic  Microb  ,  Relationship 
between  Suppuration  ;i n< I  Gangrene.  Gangrene  in  Different  Parts  of  the  Organ- 
ism.    Chemical  Analysis  of  Gangrenous  Products. 

Gangrene  is  a  morbid  process  essentially  characterized  by  the 

i no i- tifi cation  and  putrefaction  of  (issues. 

There  can  never  be  putrefaction  without  microbes.  Gangrene, 
then,  is  always  of  microbic  origin,  and  should  be  distinguished  from 
aseptic  mortifications  which  are  designated  as  necrobioses.  The 
distinction  is  not,  however,  as  sharp  as  may  appear  at  first  Bight. 
There  are  microbic  gangrenes  in  which  mortification  is  the  predom- 
inant phenomenon,  attended  by  little,  if  any,  putrefaction.  These 
are  cases  of  dry  gangrene  closely  related  to  simple  necrobioses.  In 
a  great  number  of  cases  experimental  and  bacteriological  investiga- 
tions have  not  been  sufficiently  complete  to  determine  whether  the 
process  is  due  to  an  infection  or  merely  to  cellular  disturbance.  In 
cases  of  toxic  gangrene,  like  ergotism,  or  trophic  gangrene,  like  ulcer- 
ating dermosynovitis,  it  is  not  known  whether  the  process  is  due 
simply  to  poisons  or  nervous  lesions  or  to  a  superadded  infection 
occurring  in  tissues  no  longer  capable  of  resisting  microbic  invasions. 
The  latter  view  seems  to  me  more  rational,  but  it  is  not  accepted 
by  all,  and  must  be  held  subject  to  modification. 

Gangrenes,  properly  so  called — i.  e.,  those  of  microbic  origin — 
cannot  develop  except  in  parts  which  are  in  direct  or  indirect  com- 
munication with  the  exterior.  They  are  observed  in  the  skin, 
mucous  membranes,  and  the  respiratory  apparatus.  Tissues  or 
organs  not  in  contact  with  the  air  (abdominal  viscera,  nerve  centres) 
cannot  be  the  seat  of  gangrene  unless  a  primary  focus,  whence 
microbes  may  penetrate  the  organism,  exists.  Suppose,  for  instance, 
that  the  artery  of  a  limb  is  obliterated,  gangrene  may  appear  in  the 
parts  deprived  of  circulation.     Such  is  the  case  in  senile  gangrene. 

15 


226  IXFECTIOUS  DISEASES. 

If,  however,  the  obstruction  occurs  in  a  cerebral  artery,  necrobiosis 
or  softening,  but  no  gangrene,  results. 

There  is  no  specific  microbe  of  gangrene.  The  process  is  a  com- 
monplace one,  and  what  we  said  with  regard  to  suppuration  can  also 
be  applied  to  it.  As  in  that  case,  pathogenic  agents  maybe  divided 
into  two  groups.  Some  of  them,  when  in  contact  with  healthy 
tissues,  possess  the  power  to  engender  the  two  stages  of  gangrene — 
the  mortification  of  living  elements  and  their  putrefaction.  Others 
act  only  upon  altered,  partly  mortified  tissues.  In  the  latter  instance 
pyogenic  microbes  are  found  in  the  morbid  focus,  and  they  act  upon 
the  diseased  organism  as  they  do  upon  lifeless  matter.  No  doubt, 
the  division  is  not  absolute.  The  development  of  even  the  most 
virulent  microbes  is  materially  facilitated  by  a  great  number  of 
accessory  causes,  such  as  mortification  and  chemical  alterations  of 
tissues  and  the  association  of  different  microbes.  These  conditions 
are  not  indispensable,  however,  and  occupy  a  secondary  place. 
Their  intervention  is  of  prime  importance  when  the  invading  micro- 
organisms are  of  the  kind  which  become  capable  of  giving  rise  to 
gangrene  only  on  favorable  occasions. 

Among  the  latter  are  the  pyogenic  microbes.  This  is  not  sur- 
prising, since  we  have  shown  that  in  all  suppurations  two  successive 
acts  are  to  be  distinguished:  namely,  the  necrosis  of  the  invaded 
tissue  and  the  reaction  of  the  organism,  resulting  in  the  production 
of  cells  which  make  up  the  purulent  exudate.  For  the  production 
of  the  second  phenomenon  a  certain  degree  of  reactionary  power  is 
required.  If  the  tissue  is  altered  or  the  organism  profoundly  debili- 
tated, the  necrotic  process  prevails,  and  gangrene  develops.  In 
nearly  all  instances,  however,  the  organism  makes  some  reactionary 
effort  to  eliminate  the  dead  elements,  and  suppuration  appears  sec- 
ondarily around  the  slough.  This  result  is  observed,  even  when  the 
process  is  due  to  the  specific  agents  of  gangrene,  provided  they  are 
attenuated.  The  septic  vibrio,  which  is  the  type  of  this  kind  of 
microbes,  produces  gangrene  when  very  active  or  when  inoculated 
into  susceptible  animals,  but  recedes  to  the  rank  of  a  pyogenic  when 
it  is  attenuated  or  when  the  animals  possess  a  higher  degree  of 
resistance.  In  brief,  the  pyogenic  microbes  when  exalted  become 
necrogenic;  the  neurogenic  microbes  when  attenuated  become  pyo- 
genic. 

As  we  have  already  noted,  two  stages  are  observed  in  gangrene: 
namely,  necrosis  and  putrefaction.     This  has  led  some  authorities  to. 


GANGRENE,  ill 

Gonipare  or  even  identify  gangrene  with  the  proa  oi  putrefaction 
occurring  in  the  cadaver,  The  analogy  should  nol  be  overempha- 
sized. A  dead  tissue  abandoned  to  putrefaction  do<  no1  pr< 
the  same  aspect  as  a  gangrenous  part,  and  ye1  the  microbes  developed 
maybe  identical  in  both  cases,  and  chemical  analy  i  mi 
similar  transformations  in  both  (issues.  The  difference  lies  in  the 
fact  Mini,  in  the  production  <>!'  gangrene,  ■■>  pari  i-  played  by  the 
living  elemenl  -%.  e.,  the  reactionary  process.  No  one,  however,  has 
ms  yet  attempted  to  demonstrate  the  difference  .  All  we  can  do, 
therefore,  is  to  offer  n  few  reflections  intended  to  show  how,  in  out 
opinion,  (Ik-  experiments  should  be  pursued  in  thif  connection, 

One  difference  between  putrefaction  and  gangrene  musl  depend 
upon  arrest  or  persistence  of  the  circulation,  viz.,  influx  of  blood 
serum,  lymph,  leucocytes,  and  coloring  mailers  of  the  blood.  The 
latter,  by  being  decomposed,  musl  contribute  to  the  color  of  gan- 
grenous tissue.  These  various  conditions,  however,  do  noi  suffice  to 
explain  all  phenomena:  Firstly,  because  the  circulation  is  a1  times 
interrupted,  as  in  the  case  of  dry  gangrene,  and  yet  the  pr< 
retains  its  special  character.  Secondly,  when  we  cause  putrefaction 
in  a  tissue  immersed  in  blood  we  render  the  process  .more  intense, 
but  we  do  not  produce  gangrene.  We  are  thus  led  to  the  conclusion 
that  gangrene  is  dependent  upon  the  action  of  putrefactive  proa  ss 
upon  living  cells — i.  e.,  upon  cells  capable  of  responsive  action — and 
that  the  peculiar  appearance  of  the  gangrenous  parts  is  due  solely  to 
this  cellular  reaction.  In  other  words,  cadaveric  putrefaction  is 
characterized  by  the  development  of  saprophytes  which  act  upon 
dead  matter,  viz.,  matter  incapable  of  reaction.  On  the  other  hand, 
gangrene  is  characterized  by  the  development  of  microbes  which 
attack  healthy,  sometimes  profoundly  altered  cells,  but  cells  which 
have  not  passed  into  a  state  of  vital  indifference.  Our  definition 
must,  therefore,  be  somewhat  modified,  and,  in  order  to  sharply 
distinguish  gangrene  from  cadaveric  putrefaction,  we  may  state  that 
gangrene  is  essentially  characterized  by  putrefaction  of  healthy  or  dis- 
eased but  still  living  cells. 

Causes  Favoring  the  Development  of  Gangrene. 

Even  when  gangrene  seems  to  be  primary  it  develops  only  in  deep 
wounds  which  contain,  in  addition  to  the  principal  agent,  a  multitude 
of  pyogenic  or  saprogenic  bacteria  without  the  assistance  of  which 
the  process  would  not  have  occurred. 


228 


INFECTIO  US  DISEASES. 


In  other  cases  gangrene  appears   as  a  secondary  manifestation 

either  in  the  course  of  an  infection  or  in  a  subject  suffering  from 
seme  noii-niicrobic  disease.  It  generally  develops  in  organisms 
debilitated  by  cachexia,  fatigue,  or  starvation. 

Gangrene 'at  times  first  occurs  at  a  point  of  the  economy  which 
was  sj  tared  by  the  initial  affection.  When  it  develops  in  a  locality 
that  is  already  the  seat  of  a  previous  lesion  it  represents  a  local 
epiphenomenon  superadded  to  the  pre-existing  alteration.  This  is 
observed  in  variola,  varicella,  even  vaccinia,  as  well  as  in  various 
cutaneous  affections,  such  as  purpura,  erythema  nodosum,  and 
pemphigus.  This  is  what  is  also  observed  in  mucous  membranes  and 
in  the  viscera.  A  great  number  of  necrotic  laryngites  and  ententes 
and  various  forms  of  pulmonary  gangrene  belong  in  this  group.  The 
.gangrenous  process  sets  in  and  is  assisted  by  a  previous  lesion. 

When  gangrene  appears  as  a  primary  lesion  its  development  is 
facilitated  by  all  causes  which  profoundly  disturb  the  nutrition  of 
tissues,  either  directly  (contusions,  action  of  physical  or  chemical 
agents)  or  indirectly.  In  the  latter  instance  the  influences  favoring 
the  development  of  gangrene  arise  from  vascular,  nervous,  or  humoral 
alterations — compression  and  obliteration  of  vessels,  arterites,  and 
edemas.  Symmetrical  gangrene  of  the  extremities  is  a  good  illus- 
tration of  the  role  of  nervous  alterations. 

The  following  is  a  classification  of  the  pathogenic  conditions  of 
gangrene  which,  although  artificial,  is  fairly  applicable  to  the  majority 
of  cases: 

Conditions  Predisposing  to  Gangrene. 

("Mechanical  agents. 

Physical  agents. 
I  Chemical  agents. 
[Animate  agents. 

f  Edemas. 

|  Vascular  compression  and  oblitera- 
'  Circulatory  disturbances  .  -j      tion. 

Arteritis. 
I  Arteriosclerosis. 
(  Central  alterations. 
Nervous  disturbances       .  <  Neuritis. 

(.Raynaud's  disease. 
f  Humoral    and    diathetic    affections 
(Bright's  disease,  diabetes,  etc.). 
Dystrophic  disturbances  .  -j  Autointoxications. 

Exogenic  intoxications, 
[infections. 

It  is  well  to  remark,  however,  that  in  reality  the  events  are  more 
complex  and  that  in  a  given  case  several  pathogenic  factors  usually 
intervene.  Let  us  take,  for  example,  the  phenomena  occurring  in 
cases  of  infection.  The  predisposing  cause  of  the  gangrene  is  repre- 
sented by  intoxication  of  the  organism  due  to  the  secretions  of 


Indirect  alteration  of 
tissues  by  . 


Direct    alteration    of 
tissues  by   .      . 


QANQRENE.  229 

pathogenic  microbes,  by  alterations  occurring  secondarily  in  the 
viscera  and  by  disturbances  of  cellular  metabolism.  A  a  rule, 
however,  intoxication  alone  is  tiol  sufficient.  Accounl  musl  betaken 
of  the  local  lesions  secondarily  caused  by  microbes  in  the  skin  or 
viscera  in  the  lung,  for  in  tance  ■■>  well  as  of  alteration*  mani- 
fested in  the  arteries,  capillaries,  and  nerves.  Moreover,  we  must 
not  overlook  the  fad  thai  fever  diminishe  the  ecretions,  notably 
those  of  the  mouth,  and  thai  if  the  patienl  i-  no1  properly  taken 
care  of  the  fecal  matters  and  the  urine  soil  the  orifices  and  create 
foci  of  putrefaction  which  deal  the  lasl  blow  to  the  failing  resistance 
of  the  organism.  Hence,  with  (he  progress  of  hygiene  and  antisepsis, 
secondary  gangrenes  are  of  far  less  frequenl  occurrence. 

What  has  been  stated  with  reference  to  infections  may  be  repeated 
in  regard  to  each  of  (lie  pathogenic  processes  above  admitted.  In 
every  instance  the  mechanism  is  complex.  We  shall  endeavor  to 
briefly  study  each  predisposing  cause  independently. 

Role  of  Mechanical  and  Physical  Agents.  The  important 
traumatic  mortifications  caused  by  mechanical  agents  has  been 
demonstrated  by  numerous  contributions  of  great  interesl .  In  this 
connection,  Dr.  Arloing's  remarkable  study  of  his  bacillus  hemine- 
crobiophilus  is  worthy  of  consideration.  This  microbe  is  incapable 
of  producing  gangrenous  putrefaction  in  healthy  tissues,  but  easily 
invades  tissues  altered  b}~  traumatism.  The  same  is  true  as  regards 
the  other  agents  of  gangrene.  Even  the  bacillus  of  gaseous  gangrene, 
if  freed  from  toxin  and  introduced  in  small  amount,  gives  rise  to  no 
lesion.  Lesions  are  produced,  however,  when  it  is  deposited  in  a 
muscle  that  has  been  subjected  to  violent  contusion. 

Analogous  results  occur  when  physical  agents  are  permitted  to  act 
upon  tissues.  Intense  cold  or  excessive  heat  produces  a  series  of 
cellular  mortifications.  Small  aseptic  eschars  may  result,  and  in 
connection  with  these  the  germs  of  gangrene  may  develop  and  give 
rise  to  characteristic  alterations  in  the  tissues,  as  a  consequence  of 
necrotic  lesions  or  the  formation  of  phlyctenular. 

Physical  agents,  however,  do  not  always  act  at  the  point  of  appli- 
cation. A  considerable  number  of  observations  tend  to  demonstrate 
that  exposure  to  sudden  and  intense  cold  may  induce  pulmonary 
gangrene.  In  this  instance  the  action  of  cold  is  probably  indirect. 
It  is  characterized  by  a  spasm  of  the  pulmonary  vessels  which,  caus- 
ing anemia  in  the  tissues,  rentiers  them  more  vulnerable,  and  thus 
favors  the  development  of  necrosing  agents. 


230  INFECTIOUS  DISEASES. 

Role  of  Chemical  Agents.  As  is  known,  chemical  agents  are 
divided  into  caustics  and  toxics. 

Caustics  diminish  the  resistance  of  the  tissues  and  may  even  pro- 
duce necrosis  liable  to  gangrenous  putrefaction.  This  result,  how- 
ever, is  rarely  realized,  and  the  action  of  caustics  from  the  point  of 
view  now  occupying  us  is  far  less  important  than  that  of  toxics. 

Those  toxic  substances  which  produce  gangrene  at  the  point  of 
their  introduction  are  very  much  like  caustics.  Venoms  belong  to 
this  group.  The  bites  of  snakes,  of  certain  fish,  the  sting  of  insects 
and  scorpions  may  be  followed  by  gangrenous  phlegmons.  Careful 
researches,  however,  tend  to  demonstrate  that  the  necrosis  is  due 
rather  to  the  microbes  contained  in  the  venom  than  to  the  venom 
itself.  The  venom  is  to  be  credited  only  with  the  production  of 
cellular  disturbances  which  facilitate  the  development  of  the  microbic 
agents.  The  situation  is  the  same  as  the  one  resulting  from  the 
infiltrations  of  bile  or  urine,  except  that  the  action  of  the  venom  is 
more  intense.  In  fact,  the  bile,  when  injected  beneath  the  skin  of 
a  delicate  region — for  instance,  the  ear  of  a  rabbit — produces  a 
necrosis  ending  in  the  loss  of  a  part  of  the  organ. 

The  urine  seems  to  be  less  harmful.  Its  action  is  due  chiefly  to 
the  distention  of  the  tissues  injected,  which  become  thereby  good 
culture  media  for  microbes.  The  conditions  are  the  same  as  in  the 
experiment  of  Prof.  Bouchard,  who  injected  non-sterilizecl  alimentary 
substances  beneath  the  skin  of  rabbits.  The  animals  rapidly  died 
with  gangrenous  lesions  infiltrated  with  gases.  The  subcutaneous 
fluid  swarmed  with  bacteria,  but  inoculation  of  the  latter  into 
healthy  animals  produced  no  disturbances — the  parasites  were  incap- 
able of  overcoming  the  resistance  of  a  normal  tissue. 

Role  of  Circulatory  Disorders.  Any  cause  that  diminishes  the 
nutrition  of  cells  predisposes  to  gangrene.  Samuel,  experimenting 
upon  rabbits,  produced  anemia  in  the  ear  by  ligating  the  carotid  and 
posterior  auricular  arteries.  He  then  produced  an  intense  inflam- 
mation in  both  ears  either  by  immersing  them  in  hot  water  or  by 
rubbing  them  with  croton  oil.  The  healthy  side  rapidly  returned  to 
a  normal  state,  the  anemic  side  became  the  seat  of  gangrene.  The 
writer  has  noticed  that  the  results  are  the  same  when  inflammation 
is  induced  by  means  of  the  staphylococcus.  Under  these  circum- 
stances the  anemic  part  presents  lesions  with  gangrenous  tendencies. 
Similar  facts  are  often  noted  in  clinical  observation.  Senile  gan- 
grene, which  invades  a  limb  in  which  the  artery  is  obliterated,  and 


GANGRENE.  231 

sphacelus  consecutive  to  acute  arteritis,  are  well  known  illustral 
Venous  obliterations  may  likewise  favor  the  development  of  gan- 
grene, but  less  frequently,  since  circulation  U  easily  re-<  tablished 
by  collaterals. 

Edemas,  no  matter  how  caused,  similarly  dispose  the  pari 
gangrene  by  distending  the  tissues  and  thus  disturbing  nutritive 
exchanges. 

Role  of  the  Nervous  System.  The  influence  of  the  nervous  3ystem 
in  the  pathogenesis  of  gangrene  is  beyond  question.  It  will  suffice 
to  recall  the  eschars  which  a1  I  imes  appear  so  rapidly  in  consequence 
of  some  cerebral  or  spiii.-il  lesion  and  the  cases  of  extensive  gangrene 
following  neurites,  reported  by  Pitres  and  Vaillard.  We  may  add 
Raynaud's  disease.  The  vascular  disorders  characterizing  this  affec- 
tion explain  the  pathogenesis  of  those  small  eschars  appearing  espe- 
cially in  the  fingers  and  toes — i.  e.,  at  points  where  multitudes  of 
saprophytes  swarm,  some  of  which  may  acquire  pathogenic  power. 
The  influence  of  nervous  disturbances  upon  the  development  of  gan- 
grene is  also  evidenced  by  the  experiments  pursued  by  us  with  the 
streptococcus  of  erysipelas.  Section  of  sensory  nerves  augments  the 
intensity  and  duration  of  the  lesions  and  favors  the  development  of 
gangrenous  patches. 

Role  of  Intoxications.  The  diseases  that  disturb  the  chemical 
constitution  of  the  organism,  especially  those  inducing  autoin- 
toxication, induce  gangrene  by  a  highly  complex  mechanism,  for, 
when  they  last  for  a  certain  length  of  time  they  give  rise  to  visceral 
lesions  and  arterial  and  nervous  alterations  which  contribute  to  the 
development  of  sphacelus.  Thus,  in  Bright's  disease  it  is  almost 
impossible  to  determine  the  respective  parts  played  by  the  various 
lesions  and  by  the  blood  alterations.  The  difficulty  is  equally  as 
great  in  diabetes.  The  arterial  lesions,  the  nervous  alterations,  and 
the  dyscrasie  modifications  are  alike  responsible  for  the  gangrenous 
process.  We  have  already  recalled,  in  connection  with  suppuration, 
the  experiments  of  Bujwid  and  of  Nicolas  which  demonstrate  that 
the  staphylococcus  aureus  produces  gangrene  when  it  is  inoculated 
into  a  rabbit  rendered  glycosuric  by  intravenous  injection  of  grape- 
sugar. 

The  problem  is  still  more  complex  when  we  consider  exogenic 
intoxications.  The  role  of  arterial  spasm  has  been  admitted  by  some 
authorities  to  account  for  gangrenes  produced  by  ergot.  The  experi- 
ments of  Robert  have  demonstrated  that  this  action  is  due  to  a 


232  INFECTIOUS  DISEASES. 

special  acid,  sphacelic  acid.  Is  it  to  be  assumed  that  a  spasm  renders 
the  part  anemic,  and  thus  enables  the  microbes  to  develop?  This 
explication  cannot  be  admitted  without  reserve,  since  the  experi- 
ments of  Holmes  and  of  Wernieh  tend  to  demonstrate  that  ergot  does 
not  produce  a  tetanic  state  in  the  small  arteries,  for  tension  is  lessened. 

Principal  Agents  of  Gangrene. 

Bacteriology  of  Gaseous  Gangrene.  The  type  of  microbes  capable 
of  giving  rise  to  primary  gangrene  is  represented  by  the  bacillus  of 
gaseous  gangrene,  also  called  vibrion  septique  (Pasteur),  bacillus  of 
gangrenous  septicemia,  bacillus  septicus  gangrence  (Arloing),  bacillus 
of  malignant  edema,  bacillus  ozdematis  maligni  (Flugge) . 

As  is  known,  the  microbe  in  question  is  an  anaerobic  bacillus, 
generally  occurring  in  the  form  of  motile  rods,  measuring  on  an  average 
3/i  in  length  and  1/jl  in  breadth.  It  occurs  singly  or  in  groups  of 
two  or  three,  at  times  forming  short  chains.  In  cultures  these 
bacilli  are,  as  a  rule,  solitary  and,  at  the  end  of  a  certain  length  of 
time,  form  undulating  filaments  sometimes  assuming  a  spiral  form. 
The  filamentous  forms  are  observed  in  animals,  notably  in  the  blood, 
where  they  reach  a  length  of  20/*  and  even  40/*.  They  are  easily 
stained,  but  are  decolorized  by  Gram's  method. 

The  bacillus  of  gaseous  gangrene  is  strictly  anaerobic  and  develops 
in  various  media,  provided  air  is  excluded  from  it.  The  cultures  grow 
at  68  F.  (20  C),  but  are  more  luxuriant  at  98.6  F.  (37  C).  This 
bacillus  is  pathogenic  for  man,  the  horse,  sheep,  pig,  and  guinea-pig. 
The  rabbit  is  a  little  more  resistant.     The  dog  is  rather  susceptible. 

The  symptoms  produced  in  man  have  been  described  under  the 
names  malignant  edema  (Pirougoff,  Koch),  acute  purulent  edema 
(Pirougoff),  swift  gangrene  (gangrene  foudroyante,  Maisonneuve, 
Salleron),  invading  traumatic  gangrene  (Bottini),  gangrenous  sep- 
ticemia (Chauveau,  Arloing). 

The  designation  gaseous  gangrene,  proposed  by  Poncet,  seems  to 
us  by  far  the  most  preferable.  It  has  the  advantage  of  expressing 
the  two  main  manifestations  of  the  morbid  process. 

Being  anaerobic,  this  bacillus  cannot  vegetate  in  superficial  wounds 
exposed  to  the  air.  It  invades  only  deep,  contused  wounds  contam- 
inated with  dust.  It  rapidly  develops  in  mortified  tissue,  giving  rise 
to  patches  of  sphacelus  and  an  exudation  which  exhales  a  fetid  odor 
and  is  filled  with  corrupt  gases.     At  times  the  lesion  spreads  with 


QANQBENE. 

extraordinary  rapidity  and  causes  death  within  n  few  daj  ,  with 
the  appearance  of  general  tnanifei  tation  which  clearly  Indicate  the 
profound  intoxication  of  the  organi  m,  and  are  expressed  b)  rapid 
prostration,  dyspnea,  and,  a1  the  end,  a  fall  of  temperature. 

Animals  are  liable  to  gaseous  gangrene  as  well  as  man.  A  certain 
muni ht  of  cases  have  been  reported  occurring  in  the  hor  e,  co ■■•• .  and 
rabbit,  after  traumatism  or  parturition,  Among  laboratory  animals 
the  guinea-pig  is  the  most  sensitive. 

The  results  of  numerous  experiments  demonstrate  thai  the  bacillus 
of  gaseous  gangrene  acts  the  same  as  the  saprophytes  of  putrefaction. 
The  value  of  the  author's  classification  is  thereby  diminished,  since 
this  microbe  is  not  of  itself  capable  of  overcoming  the  resistance  of 
the  organism,  although  it  is  (rue  thai  the  same  remark  holds  good 
with  regard  to  almost  all  pathogenic  agents. 

The  Various  Agents  of  Gaseous  Gangrene.  Along  with  the  bacil- 
lus of  gaseous  gangrene  are  to  be  classed  a  scries  of  microbes  which 
are  more  or  less  similar  to  it  in  their  biological  or  pathogenic 
characters. 

One  of  them  is  the  bacillus  of  symptomatic  anthrax,1  which  has 
sometimes  been  considered  a  particular  species,  sometimes  a  variety 
of  Pasteur's  bacillus.  It  differs  from  it  by  its  pathogenic  properties. 
It  attacks  mostly  cattle  and  sheep.  The  ass,  horse,  and  white  rat 
present  only  local  symptoms.  The  dog,  cat,  pig,  rabbit,  chicken, 
pigeon,  and  duck  are  refractory,  while  the  guinea-pig  is  as  sensitive 
to  it  as  it  is  to  gaseous  gangrene.  No  case  of  transmission  of  the 
disease  to  man  has  thus  far  been  reported. 

Natural  immunity,  however,  is  no  more  absolute  in  this  than  in 
other  cases.  The  author  has  demonstrated  that  it  is  possible  to 
overcome  the  resistance  of  the  rabbit  to  symptomatic  anthrax  by 
several  procedures :  namely,  by  simultaneous  injection  of  a  living  or 
sterilized  culture  of  the  B.  prodigiosus,  of  proteus  vulgaris,  or  of 
staphylococcus  aureus — by  injection  of  soluble  substances  extracted 
from  cultures  of  B.  prodigiosus  by  means  of  glycerin  and  precipitated 
by  alcohol — by  intravenous  injection  of  soluble  products  of  symp- 
tomatic anthrax,  and  by  inoculation  of  the  virus  into  the  anterior 
chamber  of  the  eye.     Finally,  as  in  the  case  of  septic  vibrio,  animals 

1  Arloing,  Comevin,  and  Thomas.  Recherches  experiment  ales  sur  la  maladie  infec- 
tieuse  appelee  charbon  symptomatique.     Revue  de  medecine.  1SS0. 

2  Roger.  Contribution  a  l'etude  experimental  du  charbon  syniptomatique.  Revue 
de  medecine,  March  and  June,  1S91. 


234  INFECTIOUS  DISEASES. 

may  easily  be  vaccinated  against  symptomatic  anthrax  by  means  of 
living  or  sterilized  cultures.  The  animals  thus  rendered  refractory 
furnish  a  germicidal  and  therapeutic  serum. 

Gaseous  gangrene  may  also  be  produced  by  other  microbes,  such 
as  the  pseudo-cedem  bacillus  of  Liborius  {B.  pseudosepticus,  Mace),. 
the  B.  phlegmones  emphysematosa  (Fraenkel),  or  B.  perfringens 
(Yeillon  and  Zuber),  which  is  an  anaerobic;  B.  cedematis  aerobicus 
of  Klein,  the  B.  pseudo-oedematis  maligna?  of  San  Felice,  and  the 
aerobic  septic  bacillus  recently  described  by  Legros  and  Lecene. 

Necrosing  Role  of  Pyogenic  Microbes.  Of  the  micro-organisms 
above  described,  several  which  produce  gaseous  gangrene  in  certain 
animals  are  simply  pyogenic  for  more  resistant  species.  Recipro- 
call}'',  common  pyogenic  germs  are  capable,  under  certain  circum- 
stances, of  creating  gangrenous  lesions. 

The  streptococcus  is  the  leader  of  those  pyogenic  germs  which 
occasionally  become  capable  of  giving  rise  to  necrosis.  This  seems 
to  be  the  microbe  causing  the  experimental  disease  which  Koch 
produced  by  inoculating  putrid  substances  into  the  mouse  and  which 
he  designated  as  progressive  necrosis.  We  have  repeatedly  stated 
that  erysipelas  produced  in  the  rabbit's  ear  by  the  streptococcus  may 
terminate  in  sphacelation.  On  the  other  hand,  injection  of  a  culture 
of  streptococcus  into  the  peripheral  end  of  the  crural  artery  in  a 
rabbit  is  at  times  followed  by  gangrene  of  the  limb.  We  must  add 
that,  under  these  conditions,  examination  of  the  mortified  parts 
shows  numerous  auxiliary  microbes,  but  these  occupy  the  most 
superficial  parts  and  evidently  play  a  role  of  secondary  impor- 
tance. 

Analogous  facts  are  observed  in  man.  Intense  erysipelas  of  the 
face  often  produces  necrosis  of  the  eyelids.  The  same  is  a  possible 
event  with  regard  to  the  testicles.  Erysipelas  may  be  followed  by 
gangrene  of  the  scrotum.  In  a  case  of  complete  sphacelation  of  the 
scrotum  the  skin  was  gradually  detached  and  the  testicles  exposed. 
This  was  then  followed  by  active  granulation,  and  the  lesion  was 
completely  repaired. 

Another  pus  coccus,  the  staphylococcus  aureus,  may  also  produce 
gangrene.  This,  like  the  streptococcus,  is  a  facultative  anaerobic. 
The  experiments  of  0.  Bujwid  establish  that  the  staphylococcus 
engenders  gangrene  in  animals  rendered  glycosuric.  Other  observa- 
tions tend  to  show,  though  not  conclusively,  that  this  micro-organism 
may  also  produce  gaseous  gangrene.     Lastly,  there  is  the  bacillus 


QANOBENE, 

proteus,  the  action  of  which  is  incontestable,    irice  il 
microbe  endowed  with  a  high  degree  of  fermentative  power. 

Gangrene  in  Various  Parts  of  the  Organism. 

Cutaneous  Gangrene.    The  majority  of  cutaneous  lesion    maybe 
complicated  by  gangrene.     No1  to  mention  anthrax  and  erysipelas, 
which  have  already  been  referred  to,  we  should  liketorecall  the 
sibility  of  gangrene  in  connection  with  the  mosl  varied  and  al  times 

the  slightest  lesions,  such  ;is  impetigo,  variola,  vaccinia,  ecthj 
herpes,  zona,  purpura,  and  even  urticaria.  Sphacelation  Lb  favored 
by  all  debilitating  causes,  and  often  coincides  with  visceral  lesions, 
diarrhea,  and  bronchopneumonia.  In  other  instances  gangrene  of 
the  sacrum  is  observed  in  the  course  of  convalescence  from  a  grave 
disease.  A  cerebral  or  spinal  lesion  is  at  times  responsible  for  the 
gangrenous  process.  If  is  readily  conceivable  that,  under  these 
various  conditions,  the  pus  cocci  and  saprophytei — aormal  residents 
of  the  skin — may  easily  develop  and.  by  their  association,  create 
gangrene. 

Gangrene  of  the  Limbs.  Instead  of  remaining  limited  to  the  Bkin, 
gangrene  may  invade  a  more  or  less  considerable  part  of  a  limb. 
This  is  notably  observed  in  the  course  of  acute  arterites  consecutive 
to  infectious  diseases.  The  lesion  is  due  to  the  obliteration  of  the 
vessel  by  a  microbe — the  streptococcus  in  the  majority  of  instances. 
The  ischemia  resulting  therefrom  leaves  the  tissues  in  a  stal 
absolute  impotence  against  the  toxins  secreted  by  the  pathogenic 
agent  and,  incidentally,  against  the  microbes  tending  to  penetrate 
the  skin. 

An  affection  which  we  have  endeavored  to  individualize  under  the 
name  benign  gangrene  of  the  eyelids1  is  related  to  gangrenous  1<  - 
of  the  skin.     The  germ  concerned  in  the  lesion  was  a  large  micro- 
coccus, staining  by  Gram's  method,  and  developing  preferably  in 
aerated  media. 

Gangrene  of  the  Mammary  Glands.    Although  the  word  gangrene 
immediately  suggests  the  idea  of  a  grave  process,  we  have  ah 
referred  to  cases  in  which  the  evolution  is  favorable  and  even  be- 
nign, as  is  often  the  case  with  gangrene  of  the  eyelids  and  genital 
organs.     The  same  is  true  with  regard  to  gangrenous  mammitis. 

Investigations  in   comparative   pathology  have  shown  the  fre- 

1  Roger  and  Weil.     Gangrene  benisrne  tics  paupieres.     Presse  medieale.  1 


236  I  WFEl '  TH '  I 'S  DISEASES. 

quency  of  gangrenous  mammitis  in  milk  yielding  females,  notably 
among  bovidse.  In  a  great  number  of  cases  the  presence  of  strepto- 
cocci of  peculiar  characters  has  been  reported.  Kitt,  Lucet,  and 
Guillebeau  have  described  other  pathogenic  agents.  No  researches 
having  been  pursued  as  to  the  human  species,  reference  must  be  made 
to  a  case  which  the  author  studied  with  Dr.  Gamier.1  A  woman,  aged 
seventeen  years,  had  been  confined  on  March  1,  1899.  The  child  had 
died  two  days  later,  without  any  definite  cause.  On  March  7th  she 
complained  of  malaise  and  pain  in  the  throat.  On  the  9th  a  typical 
scarlatinal  eruption  appeared  upon  her  body  and  she  was  imme- 
diately sent  to  the  isolation  hospital  of  la  Porte  d'Aubervilliers. 

From  the  time  of  her  admission  the  state  of  her  left  mamma 
attracted  our  attention.  The  skin  of  the  region  presented  a  diffuse 
redness,  especially  marked  toward  the  internal  and  lower  part,  where 
two  patches  of  ulceration  with  sphacelated  base  were  noted.  There 
was  abundant  fetid  discharge.  Other  smaller  ulcers  developed 
around  the  areola.  The  gland  itself  was  swollen  and  very  painful 
on  palpation. 

Moist  dressings,  constantly  applied  to  the  diseased  region,  in  no 
way  modifying  the  condition,  the  odor  of  the  purulent  discharge  soon 
became  plainly  gangrenous ;  the  lesion  itself  began  to  spread,  and  the 
ulcerations  assumed  a  dark  color.  We  then  prescribed  dressings  with 
peroxide  of  hydrogen.  Improvement  was  immediately  manifest.  A 
grayish  eschar  separated,  eliminating  the  mortified  glandular  tissue. 
Three  weeks  after  the  beginning  of  the  disease  cicatrization  was 
completed. 

The  pus  taken  from  the  wound  was  examined  and  cultured  in 
various  media.  Several  series  of  inoculations  with  the  pus  were  made 
into  rabbits  and  guinea-pigs,  for  which  it  proved  pathogenic;  less 
so,  however,  for  the  latter  than  the  former.  The  predominating 
microbe  was  a  small  micrococcus  whose  clearly  rounded  elements 
were  usually  solitary,  sometimes  associated  in  couplets,  and  excep- 
tionally forming  groups  of  three.  They  were  free  among  the  cells, 
and  none  were  found  inside  the  leucocytes.  In  addition  to  this 
microbe,  some  chains  of  streptococci  were  observed,  but  they  were 
comparatively  few  in  number. 

The  results  obtained  by  the  several  series  of  inoculations  were 
sufficiently  uniform  to  demonstrate  that  the  microbe  isolated  by  us 

1  Roger  and  Gamier.  Note  sur  un  cas  de  mammite  gangreneuse.  Lapresse  medicate* 
July  22,  1899. 


GANGRENE.  237 

was  a  pathogenic  agent,  capable  of  giving  rise  to  grave  and  < 
suppurative  lesions.    The  developmenl  of  the  gangrenou    mammitu 
may,  it  seems  to  us,  be  legitimately  attributed  to  thi  microbe. 

The  micrococci  round  in  the  gangrenous  mammifa  of  milk  yielding 
females  may  be  compared  to  the  one  isolated  by  us  in  the  human 
subject,  but  the  comparative  study  which  we  have  pur  ued  -hows 
that  our  microbe  preserves  its  own  individuality.  I'-  cultural  char- 
acters and  its  pathogenic  action  upon  laboratory  animate  do  not 
permit  its  confusion  with  other  species  already  described. 

Gangrene  of  the  Mouth  and  its  Adnexse.  There  i  an  affection 
of  the  mouth  which  may  be  looked  upon  as  a  superficial  and  benign 
gangrene.  We  refer  to  what  is  improperly  designated  as  ulcerative 
membranous  stomatitis.  In  reality,  the  so-called  false  membrane  b 
nothing  more  11  inn  I  lie  mortified  mucous  membrane.  .Many  authori- 
ties have  studied  this  affection  with  the  view  of  detecting  a  specific 
microbe,  but  with  no  encouraging  results.  Pasteur  and  Netter 
observed  the  presence  of  spirilla  in  the  patches.  Fri'ihwald  noticed 
the  same  elements  associated  with  cocci,  bacilli,  and  filament-  of 
leptothrix.  According  to  Gallipe,  the  probabilities  are  thai  there  is 
no  specific  microbe  and  that  the  disease  is  created  by  buccal  sapro- 
phytes which  have  become  exalted  by  various  causes — the  evolution 
of  a  wisdom  tooth,  for  instance.  However,  the  researches  of  Vincent, 
by  proving  that  chancriform  tonsillitis  is  due  to  the  combined  act  inn 
of  the  spirilla  of  the  mouth  and  fusiform  bacilli,  give  a  certain  value 
to  the  older  researches  of  Netter. 

The  true  gangrene  of  the  mouth — noma — is  one  of  the  affections 
which  has  become  rare,  owing  to  the  progress  of  antiseptic  practice. 
As  early  as  1878  Sanson  noticed  in  the  blood  the  presence  of  microbes, 
but  these  were  in  nowise  pathogenic.  Jordan  and  Morse  made 
similar  observations.  During  an  epidemic  of  measles  raging  jn 
Munich,  Ranke  had  the  opportunity  to  study  six  cases  of  noma. 
Microscopic  examination  revealed  numerous  microbes,  particularly 
diplococci  and  streptococci,  but  inoculation  into  the  rabbit  produced 
no  result.  By  examining  sections  of  tissues  preserved  in  alcohol, 
Rossi  found  masses  of  rods,  staphylococci,  streptococci,  and  lepto- 
thrix. The  results  were  analogous  in  a  case  studied  by  Babes,  who 
encountered  leptothrix,  spirilla,  the  streptococcus  pyogenes,  the 
staphylococcus  aureus,  and  an  ovoid  bacillus.  In  a  more  recent 
contribution  Babes  announced  that  he  had  isolated  a  very  slender 
bacillus  whose  cultures  injected  into  the  cheek  of  a  rabbit  produced 


238  IXFECTIO  US  DISEASES. 

a  gangrene  similar  to  noma.  This  highly  interesting  result  is  to  be 
classed  with  that  obtained  by  Schimmelbusch.1  In  the  case  reported 
by  the  latter  authority  there  were  found  at  the  centre  of  the  eschar 
a  multitude  of  various  microbes.  At  the  periphery,  however,  there 
were  none  but  slender  bacilli,  with  rounded  extremities,  occurring 
singly  or  in  couplets,  and  capable  of  growing  into  filaments.  Inocu- 
lation of  either  the  cultures  or  the  mortified  tissue  into  the  rabbit 
produced  only  abscesses.  In  two  chickens  patches  of  necrosis  devel- 
oped and  were  healed  in  three  weeks. 

Gangrenous  angina  is  not  always  connected  with  the  diphtheritic 
process.  It  may  be  primary.  Excluding  the  cases  of  superficial 
gangrene,  however,  which  are  related  rather  to  the  study  of  pseudo- 
membranous anginas,  true  gangrenous  angina  is  a  rarity.  Out  of  a 
total  of  701  observations,  the  author  has  collected  but  three  cases. 

Gangrene  of  the  Respiratory  Apparatus.  Two  varieties  of  gan- 
grenous processes  may  be  distinguished.  One,  comparatively  benign 
and  often  curable,  in  which  the  superficial  lesion  remains  limited  to 
the  bronchi;  the  other,  profound,  invading  the  parenchyma. 

In  cases  of  fetid  bronchitis  the  most  varied  microbes  have  been 
found.  Rosenstein  met  with  the  oidium  albicans;  Canalis,  with 
actinomycetes ;  Ley  den  and  Jaffe,  with  the  leptothrix  pulmonalis. 
Lancereau  observed  diplococci;  Marfan,  the  bacterium  termo,  and 
Noica,  the  colon  bacillus.  One  of  the  best  studied  observations  is 
that  of  Lumnitzer.  He  found  four  staphylococci:  the  S.  albus, 
citreus,  cereus  flavus,  and  cereus  albus;  one  diplococcus,  and  one 
bacillus.2 

Pulmonary  gangrene  has  much  oftener  been  the  subject  of  bac- 
teriological researches.  As  early  as  1846  Virchow  noticed  in  the 
gangrenous  fluids  the  presence  of  sarcina  resembling  those  found 
in  the  stomach.  Fischer  collected  eighteen  observations  of  this  kind, 
four  of  which  are  his  own. 

The  most  recent  contributions  show  that  the  most  varied  microbes 
may  be  encountered  in  the  foci  of  pulmonary  gangrene.  Those  most 
frequently  found  are  the  buccal  spirillum,  the  proteus  vulgaris,  the 
streptococcus,  the  staphylococcus  aureus,  tetragenus,  and  the  lepto- 
thrix.    Moreover,  various  pathogenic  bacteria  may  be  met  with 

1  Schimmelbusch.    Ein  Fall  von  Noma.    Deutsche  med.  Wochenschrift,  1889,  No.  26. 

2  iAimnitzer.  Adatok  a  rothaszto  horglob  koroktana  es  tiinettanahoz  (contribution 
to  the  etiology  and  symptomatology  of  putrid  bronchitis).  Orvosi  Hetilap,  1888  (Anal. 
Central,  f.  Bakteriologie,  1888,  Bd.  iii.  p.  621). 


GANGRENE, 

which  vary  from  one  case  to  anol  her.  ( ruillemol ,'  who  ha  reported 
the  results  of  his  studies  in  thirteen  cases  of  pulmonary  gangrene, 
attributes  an  importanl  rdle  to  anaerobic  microbes  in  the  production 

of  the  process,  and  regards  them  even  indii  pen  able.  Ii  i-  true, 
however,  that  these  anaerobic  agents  are  nol  highly  virulent.    They 

must  be  inoculated  in  I  urge  doses  or  associated  with  other  species, 
notably  to  aerobics,  in  order  to  give  rise  to  morbid  phenomena. 

In  two  of  the  author's  cases,  one  observed  in  L885  the  other  in 
1895,  the  pulmonary  gangrene  seemed  to  have  been  produced  by 
saprophytes  developed  in  a  primary  focus  created  by  the  pneumo- 
coccus  or  streptococcus.  In  both  cases,  however,  these  cocci  had 
rapidly  lost  their  virulence  and  had  done  no  more  than  prepare  the 
soil  for  the  developmenl  of  putrefactive  agents.  However  thai  may 
be,  the  pyogenic  micro-organisms  seem  to  play  an  importanl  role. 
Issuing  from  a  purulent  focus,  they  have  been  known  1o  be  mi 
in  the  lung  and  there  form  the  starting  point  of  a  gangrenous  lesion. 
Bonome,  who  had  the  opportunity  to  examine  nine  cases  of  pulmon- 
ary gangrene,  found  the  streptococcus  five  times,  the  staphylococcus 
three  times,  and  once  the  two  species  together. 

Babes  also  found  the  staphylococcus  aureus  in  a  case  of  pulmonary 
gangrene.  This  micro-organism  was  associated  with  a  bacillus  which 
produced  a  general  infection  and  which  the  author  described  under 
the  name  proteus  lithalis.  The  latter  appears  in  the  form  of  small 
rods,  measuring  from  0.8/*  to  1.5/*,  at  times  growing  as  filaments. 
It  is  a  motile,  facultatively  anaerobic  microbe.  Subcutaneous  inocu- 
lation gives  rise  to  considerable  edema  and  causes  death  in  suscep- 
tible animals — mouse  and  rabbit — in  two  or  three  days. 

In  a  case  of  pulmonary  gangrene  which  came  under  observation 
of  the  author  in  1900,  the  morbid  manifestations — cerebral  symp- 
toms, difficult  and  slow  response  to  questions,  jerky  delivery — led 
him  to  think  of  some  cerebral  localization  of  the  germs  which  had 
•primarily  affected  the  intestines.  The  necropsy  did  not,  however, 
reveal  any  appreciable  lesion  of  the  nerve  centres,  except  a  slight 
serosanguinolent  edema  of  the  meninges.  Except  the  intestines,  the 
abdominal  organs  presented  nothing  special.  To  come  to  the  inter- 
esting point,  however,  on  continuing  the  necropsy,  the  right  inter- 
lobular fissure  was  found  closed  with  soft,  recent  adhesions.  In  the 
upper  part  of  the  lower  lobe  of  the  lung  was  discovered  a  large  pouch, 
the  walls  of  which  were  2  cm.  to  3  cm.  thick,  containing  about  100 

1  Guillemot.     Recherche  sur  la  gangrene  pulmonaire .     These  de  Fari~.  1S99. 


240  INFECTIO I  ft  DISEA SES. 

grams  (over  3  ounces)  of  a  fluid  exhaling  a  fetid  odor.  The  sac 
was  perfectly  closed.  The  cavity  was  crossed  by  a  bronchus,  but 
no  opening  was  found — a  fart  which  accounts  for  the  absence  of  all 
pulmonary  sjmiptoms. 

The  data  of  the  necropsy  disclose  the  succession  of  the  pathological 
events.  In  order  of  date,  the  intestinal  incidents  were  the  first,  and 
the  pulmonary  lesion  took  its  origin  in  the  lesion  in  the  alimentary 
canal. 

The  microscopic  examination  of  the  fluid  showed  innumerable 
bacteria.  I  shall  confine  myself  to  mentioning  streptococci,  large 
micrococci,  diplococci  resembling  those  of  pneumonia,  bacilli  recall- 
ing the  anthrax  bacillus,  and  very  slender  bacilli  which  were  often 
united  in  masses. 

The  various  observations  briefly  reported  above  show  that  the  foci 
of  pulmonary  gangrene  contain,  as  a  rule,  pneumococci  or  pyogenic 
germs  associated  with  saprophytes.  The  latter  may  acquire  no 
virulence,  as  is  proved  by  the  negative  results  at  times  obtained  by 
inoculating  the  gangrenous  fluid  directly  into  animals  and  by  employ- 
ing the  cultures,  or  else  they  become  exalted  and  pathogenic.  In  the 
latter  instance  gangrene  is  inoculable  into  animals,  and  its  trans- 
mission to  man  is  then  conceivable.  It  is  to  be  noted,  however,  that 
while  the  virulence  of  these  necrosing  agents  is  generally  very  ener- 
getic, their  development  cannot  occur  in  healthy  subjects.  In  obser- 
vations upon  the  contagion  of  pulmonary  gangrene,  the  contaminated 
individuals  had  already  been  suffering  from  respiratory  affections. 
Pulmonary  gangrene  is  almost  always  the  result  of  autoinfection. 

The  relative  frequency  of  the  various  causes  of  pulmonary  gan- 
grene clearly  appears  in  the  statistics  of  Hensel,1  according  to  whom 
the  most  frequent  causative  lesion  is  embolism,  represented  by  20 
cases.  Of  these  20  cases,  9  were  pyemic  emboli.  Then  follow  the 
other  causes:  pneumonia,  14  times;  tuberculosis,  11  times;  carcino- 
mata  in  the  neighborhood  of  the  lungs,  10  times;  bronchiectasis,  5 
times;  cerebral  affections,  5  times;  traumatism,  3  times.  Lastly,  in 
three  other  instances,  the  lesions  discovered  were  a  perforation  of  the 
esophagus  and  an  abscess  of  the  mediastinum — a  focus  of  actinomy- 
cosis— and  suppurations  of  puerperal  origin. 

Gangrenous  and  Fetid  Pleurisies.  Pleurisies,  the  exudation  of 
which  is  characterized  by  a  putrid  odor,  are  commonly  divided  into 

1  Hensel.  Beitrage  zur  Casuistik  des  Lungenbrandes.  Deutsches  Archiv  f.  klin. 
Medicin,  Bd.  xli.  p.  185. 


GANGRENE.  241 

two  groups:  gangrenous  pleurisies  consecutive  t"  sphacelation  of 
pulmonary  tissue,  and  fetid  or  putrid  pleuri  "    {pleur&  ><■  ozSneu  < 
of  Dieulafoy),  which  are  produced  in  the  absence  of  any  primary  i 
in  the  subjacent  organ.     In  the  former  ca  6  we  have  to  deal  with  a 
lesion  created  by  propagation  or  rather  contiguity.    The  pathogenic 
germs  have  reached  the  pleura  after  invading  the  lung  and  engen- 
dering a  more  or  less  extensive  gangrene  in  its  parenchyma,     In  the 
latter  instance,  the  microbes  may  possibly  have  penetrated  l>;. 
of  the  bronchi  and  the  lungs,  t  raversing  these  organs  without  altering 
them.     More  frequently  they  are  derived  from  another  region  of  the 
organism,  particularly  from  the  alimentary  canal.     Dieulafoy  hae 
justly  laid  stress  upon  (he  frequency  and  gravity  of  appendicular 
pleurisies. 

This  at-  present  classical  distinction  seems  to  lie  in  harmony  with 
the  etiology  and  pathological  anatomy  of  the  lesions.  From  the 
pathogenic  standpoint,  however,  the  division  referred  to  is  less  exact. 
Whatever  the  variety  under  observation  may  be,  the  same  microbes 
are  always  met  with — common  pyogenic  agents  associated  with 
.saprophytes  or  numerous  aerobic  or  anaerobic  bacterial  species. 
In  fact,  the  pneuniococcus,  the  streptococcus,  the  staphylococcus, 
the  tetragenus,  the  colon  bacillus,  B.  proteus  vulgaris,  leptothrix, 
bacillus  of  gaseous  gangrene,  the  spirillum  of  the  saliva,  the  B. 
ramosus,  the  B.  perfringcns,  and  the  staphylococcus  parvuhis  have 
been  found  in  the  pleural  fluid. 

Gangrene  of  the  Alimentary  Canal,  Liver,  Spleen  and  Genital 
Organs.  The  great  number  of  microbes  swarming  in  the  digestive 
tract  explains  the  frequency  of  gangrenous  lesions  observed  therein. 
In  most  cases,  however,  gangrenes  are  superficial  and  at  the  necropsy 
appear  under  the  form  of  simple  ulcerations.  On  the  other  hand. 
true,  deep,  invading  gangrene  is  quite  rare.  It  is  observed  especially 
as  a  result  of  hernial  or  internal  strangulations,  by  preference  in 
intestinal  invaginations,  as  well  as  a  complication  of  typhlitis  and 
appendicitis,  exceptionally  as  a  result  of  thrombosis  of  the  mesenteric 
artery.1  No  precise  bacteriological  examinations  have  been  made  in 
such  cases.  We  are  not  any  better  informed  as  to  the  superficial 
gangrenes.  The  type  of  the  kind  is  represented  by  dysentery.  Even 
though  the  etiological  role  of  the  ameba  be  admitted,  it  is  not  known 
what  part  is  played  by  the  various  microbes  of  the  digestive  canal. 

1  Adenot.  Thrombose  de  l'artere  mesenterique  inferieure  et  gangrene  du  c61on. 
Revue  de  medecine,  1890. 

16 


242  INFECTIOUS  DISEASES. 

The  putrid  germs  may  pass  from  the  intestine  into  the  liver  and 
there  produce  gangrenous  abscesses.  This  is  not  an  uncommon 
occurrence  in  dysentery.  The  primary  lesion  is  sometimes  so  small 
as  to  escape  notice,  as  is  proved  by  an  observation  of  Straus.1  The 
liver  was  the  seat  of  numerous  gangrenous  abscesses  the  pus  of  which 
was  mixed  with  fetid  gases.  The  spleen  also  contained  a  purulent 
focus  characterized  by  gangrenous  odor,  including  detritus  of  spha- 
celated tissue.  Numerous  microbes,  which  could  not  be  cultivated, 
were  seen  in  the  sections. 

These  various  lesions  of  the  intestine  and  its  adnexse  may,  of 
course,  extend,  to  the  peritoneum. 

We  have  alreacty  referred  to  gangrene  of  the  genital  organs,  and 
stated  that  in  the  male  the  external  parts  may  become  the  seat  of 
gangrene  consecutive  to  genital  erysipelas  and,  in  some  cases,  of 
spontaneous  gangrene  characterized  by  an  amazingly  rapid  course. 
In  the  latter  case  large  numbers  of  streptococci  are  found  associated 
with  anaerobic  germs. 

Chemical  Characters  and  Toxic  Power  of  Gangrenous  Products. 

Chemical  analyses  of  gangrenous  products  have  demonstrated  that 
the  amount  of  water  increases  considerably  in  moist  gangrene. 
Carbon  diminishes,  while  it  is  augmented  in  dry  gangrene  (Raynaud 
and  Reveil).  Albumins  are  broken  up,  and  yield,  on  the  one  hand, 
leucin  and  tyrosin;  on  the  other,  fatty  acids  which  are,  in  some 
instances,  sufficiently  abundant  to  impart  an  acid  reaction  to  the 
gangrenous  fluid.  These  acids  are  mostly  represented  by  butyric 
and  valerianic  acids  which  give  the  focus  its  fetid  odor.  There  are 
also  found  gases,  such  as  sulphuretted  hydrogen  and  ammonia. 

These  various  transformations  are  evidently  related  to  the  multi- 
plication of  microbes,  and  are  due,  in  part  at  least,  to  the  soluble 
products  or,  more  precisely,  to  the  ferments  secreted  by  the  microbes. 
This  is  demonstrated  by  the  investigations  of  Filehne,  Stolnikow, 
and  Escherich,  who  found  in  the  sputa  of  patients  suffering  from 
pulmonary  gangrene  a  ferment  which  is  similar  to  trypsin  and 
possesses  the  property  of  dissolving  even  elastic  fibres. 

Coincidently  with  the  evolution  of  the  local  lesions  are  observed 
a  series  of  general  phenomena  of  a  serious  character.     Most  of  these 

1  Straus.  Sur  un  cas  d'abces  gangreneux,  probablement  primhif,  du  foie  et  de  la 
rate.     Archives  de  med.  exp.,  May,  1896,  p.  428. 


GANGRENE.  243 

may  be  ascribed  to  the  microbic  products,  In  fact,  we  '.now  that 
the  Foci  almost,  ciiii;'.i:ini l\  <•< ,i 1 1 ; i i i j  pyogenic  cocci,  of  which  we  have 
already  studied  the  toxins,  and  we  have  further  pointed  oul  that 
very  active  substances  are  secreted  by  the  bacillus  of  ga  eom  gan- 
grene and   I, lie  oilier  necrosing  agent  , 

Some  have  recently  attempted  to  belittle  the  rdle  of  pyogenic  . 
and  Veillon,  to  whom  we  owe  such  valuable  contributions  upon 

anaerobic-  bacteria,  has  contended  thai  gangrene  i  always  due  to 
anaerobic  germs.  This  seems  to  the  author  to  be  an  exaggerated 
statement.  The  author  thinks  that  along  with  the  stricl  anaerobics, 
the  influence  of  which  has  so  well  been  proven  by  Veillon  and  his 
collaborators,  must  be.  classed  certain  microbes  capable  of  living  in 

the  presence  as  well  as  in  the  absence  of  air.      ft    is  also  to  be  QOted 

that  putrid  decompositions  are  not  always  affected  by  strictly  anae- 
robic microbes.  The  colon  bacillus  is  a  first-class  put  refactive  agent . 
To  be  convinced  of  this,  it  suffices  to  smell  the  odor  of  certain 
cultures.  The  author  would  therefore  state,  in  conclusion,  thai  gan- 
grene is  a  common  process  to  which  most  varied  microbe-,  either 
strictly  or  facultative  anaerobics,  may  give  rise.  Of  these  microbes 
a  few  are  endowed  with  a  high  degree  of  pathogenic  power,  but  this 
is  an  exception.  Most  of  them  are  no  more  than  putrefact  ive  agents 
incapable  of  developing  in  healthy  tissues.  They  multiply  only  in 
those  parts  of  the  organism  which  have  been  altered  by  previous 
processes.  They  are  able  to  induce  grave  manifestations  by  virtue 
of  the  putrid  poisons  secreted  by  them.  They  are  toxicogenetic 
rather  than  infectious,  and  this  is  the  reason  the  inoculation  of 
gangrenous  products  often  gives  rise  to  no  disturbance  whatever. 


CHAPTER    IX. 

SEPTICEMIAS  AND  PYEMIAS. 

Definition  of  Words:  Septicemias,  Pyemias,  Bacteremias,  Bacteriotoxemias.  Con- 
secutive and  Secondary  Cryptogenetic  Bacteremias.  Septicemic  Forms  of  Infec- 
tions or  Specific  Septicemias.  Agents  of  Septicemias  and  Pyemias.  Experi- 
mental Septicemias  and  Pyemias.  Septicemias  of  Animals.  Hemorrhagic 
Septicemias.  Study  of  the  Epizootic  Rhinitis  of  the  Rabbit.  Application  of 
Researches  of  Experimental  and  Comparative  Pathology  to  Human  Pathology. 
Principal  Clinical  Characters.  Evolution.  Importance  and  Frequency  of  Atten- 
uated Forms.  Variolic  Pyemia  and  Septicemia.  Experimental  Researches  on 
the  Parasite  of  Smallpox;  its  Culture  and  Inoculabilitjr. 

Definitions  and  Divisions  of  Septicemias  and  Pyemias.  Septi- 
cemia and  pyemia  constitute  two  morbid  processes  which  must  be 
drawn  nearer  and  united  under  the  comprehensive  term  bacteremia. 
In  reality,  the  pathogenic  germ  either  invades  the  whole  organism 
without  creating  special  lesions  (septicemia),  or  it  locates  itself  in 
certain  viscera  or  tissues,  and  gives  rise  to  the  formation  of  purulent 
feci  (pyemia).  In  the  latter  instance  a  considerable  number  of  small 
abscesses  are  generally  found  at  the  necropsy  occupying  the  liver, 
kidneys,  lungs,  heart,  etc.;  these  are  designated  by  the  rather  im- 
proper name  metastatic  abscesses. 

Bacteremia  must  be  distinguished  from  bacteriotoxemia  in  which 
the  pathogenic  agent  remains  localized  and  gives  rise  to  general 
manifestations  by  means  of  the  toxins  it  secretes.  In  bacteremia 
there  is  general  infection;  in  bacteriotoxemia,  intoxication. 

Bacteremia,  then,  includes  both  septicemia  and  pyemia.  The 
expression  septicemia,  created  by  Piorry,  was  to  be  applied  to  all 
alterations  of  the  blood  produced  by  septic  or  putrid  substances, 
whatever  their  origin.  After  having  been  employed  in  most  diverse 
senses,  the  term  was  adopted  by  bacteriologists  who  have  not  suc- 
ceeded in  defining  it  any  better  than  clinicians.  Confusion  was  fur- 
ther increased  when  the  bacillus  of  gaseous  gangrene  was  called 
septic  vibrio,  and  the  disease  induced  by  it  gangrenous  septicemia. 
These  improper  terms  led  to  important  errors  and  nosological  con- 
fusion. Thus,  for  example,  deceived  by  these  words,  some  authors 
believed  that  septicemia  and  pyemia  should  be  separated  on  the 


SEPTICEMIAS  AND  PYEMIAS.  245 

ground  of  thedifferent  characters  of  their  pathogenic  agenl  .   Ace 
ing  to  the  expressions  used  by  bacteriologists,  septicemia  was  due 
to  an  anaerobic  bacillus,  namely,  septic  vibrio,  remaining  a1   the 
point  of  introducl  ion;  pyemia  was  dependenl  upon  aerobic  microbes 
invading  the  organism  and  there  producing  secondary  absce    i   . 

As  a  matter  of  course,  a  word  may  be  employed  in  thi 
attributed  to  it  by  an  authority,  provided  il  be  well  defined.  Hence, 
the  term  "septicemia"  might  be  reserved  for  gaseous  gangrene  and 
analogous  processes.  This,  however,  would  be  a  notable  departure 
from  the  prevailing  tendency,  since,  logically,  il  would  be  nece 
to  consider  all  local  diseases  which  kill  by  intoxication  as  septicemias, 
and  thus  include  tetanus,  diphtheria,  cholera,  etc.,  in  this  group:  In 
these1  infections,  as  in  the  case  of  gaseous  gangrene,  the  microbes 
remain  localized  at  one  point,  and,  as  their  soluble  secretions  arouse 
general  reactions,  the  disease  is  of  a  toxic  character.  This  is  why 
these  diverse  processes  constitute  a  separate  group  — bacteriotoxemias 
— and  why  gangrenous  septicemia  must  be  excluded  from  the  group 
of  true  septicemias.  Thus  limited,  bacteremias  still  represent  an 
artificial  nosological  class;  their  existence  may,  nevertheless,  be 
rendered  legitimate  by  the  following  considerations: 

In  cases  of  septicemia  the  microbe  is  present  in  every  part  of 
organism;  it  may  often  be  detected  in  the  blood  during  life, 
always  after  death.  The  lesions  are  those  common  to  all  grave 
infections.  The  blood  is  disintegrated  and  dark  in  color:  numerous 
ecchymoses  are  found  in  the  viscera  and  tissues.  Hemorrhages  are 
at  times  so  profuse  that  the  affection  deserves  to  be  designated  as 
hemorrhagic  septicemia.  The  microscope  reveals  small  vascular 
thromboses,  cellular  degenerations,  and  occasionally  embryonic  foci, 
indicating  a  reactionary  tendency  on  the  part  of  the  organism.  Tin  se 
foci  are  limited,  however,  and  are  not  visible  to  the  naked  eye. 

At  the  end  of  a  variable  period  of  time,  however,  the  microbes 
become  localized  at  certain  points  of  the  economy:  septicemia  then 
loses  the  character  of  a  general  infection,  and  visceral  localizations 
become  predominant  features.  The  secondary  foci  then  appearing 
are,  in  some  cases,  simple  inflammatory  lesions:  in  other  instances 
they  undergo  purulent  transformation.  Under  these  conditions  the 
process  might  properly  be  designated  as  septicopyemia,  representing 
a  transitional  form  between  septicemia  and  pyemia. 

Pyemias  are  distinguished  from  septicemias  by  the  tendency  of 
the  infectious  agent  to  localize  itself  from  the  beginning  in  certain 


246  I. X FACTIOUS  DISEASES. 

viscera  or  tissues  and  there  give  rise  to  purulent  foci.  The  germs 
transported  by  the  blood  quickly  leave  this  medium;  hence  the 
assertion  of  some  authors  that  in  true  pyemia  the  microbes  are  found 
exclusively  in  the  tissues.  When  they  are  at  the  same  time  encoun- 
tered in  the  blood,  the  process  should  be  held  to  be  septicopyemic. 
We  shall  see  that  this  latter  distinction  is  not  well  founded. 

While  septicemias  and  pyemias  may  produce  anatomical  lesions, 
they  may  also  be  consecutive  to  some  local  lesion.  According  to 
their  apparent  point  of  origin,  two  varieties  may  be  admitted.  The 
first  is  characterized  by  invasion  at  once  of  the  entire  organism ;  the 
portals  of  entrance  of  the  microbe  and  the  initial  lesion  are  wanting 
or  remain  unperceivecl.  The  infection  is  then  said  to  be  spontaneous 
or  cryptogenetic.  The  latter  epithet,  introduced  by  Leube  and 
accepted  by  Jurgensen,  is  now  frequently  employed  in  Germany. 
In  the  second  variety,  general  infection  is  preceded  by  a  local  lesion. 
Here  two  events  are  possible :  sometimes  the  primary  focus  contains 
the  microbes  which  subsequently  invade  the  economy,  in  which 
instance  bacteremia  deserves  the  name  consecutive ;  sometimes,  on 
the  contrary,  the  primary  focus  is  the  work  of  specific  or  non-specific 
agents  which  do  no  more  than  provide  a  portal  of  entrance  for  the 
microbe  of  general  infection,  in  which  case  bacteremia  is  said  to  be 
secondary. 

According  to  the  foregoing  considerations,  we  may  classify  the 
various  types  of  septicemic  and  pyemic  infections  as  follows : 

Classification  of  Septicemias  and  Pyemias. 

According  to  Their  Origin.  According  to  Their  Evolution., 

Primary:  Without  special  localization  (true  septi- 

Traumatic.  cemias). 

Cryptogenetic. 
Consecutive.  With  inflammatory  visceral  localizations. 

Secondary.  With  suppurative  localizations: 

Septicopyemias . 
Pyemias. 

May  general  infection  ever  be  truly  primary  or,  on  the  contrary, 
is  it  always  consecutive  to  a  local  lesion,  such  lesion  being  in  some 
cases  so  minute  as  to  escape  detection?  The  latter  eventuality  is 
frequently  realized.  On  the  other  hand,  the  reality  of  primary  gen- 
eral infections  seems  to  be  demonstrated  by  numerous  surgical  obser- 
vations and  experimental  researches.  Clinically,  disturbances  have 
been  seen  to  develop  in  consequence  of  an  accidental,  an  operative, 
or  an  obstetrical  wound  which  seemed  in  good  condition.    The  same 


8EPTI0EMIA8  AND  PTEMIA8.  247 

is  true  with  regard  to  animals.  When  an  extremely  virulenl  microbe 
a  certain  streptococcus,  for  instance,  i  inoculated  beneath  the  -kin, 
death  supervenes  from  bacteremia  withoul  the  slightesl  local  lesion. 
Furthermore,  under  a  greal  number  of  circumstances,  the  microbes 
which  we  carry  normally,  notably  those  of  the  alimentary  canal,  i 
penetrate  into  the  economy,  and,  under  debilitated  conditions  of  the 
system,  they  may  a1  once  induce  a  general  disease.  In  Buch  i 
it  is  impossible  to  find  a  trace  of  their  passage,  for  no  lorn!  lesion 
exists,  [f  it  were  always  possible  to  determine  the  mechanism  of  the 
infection,  occurrences  of  this  kind  should  be  grouped  under  the  name 
autobacleremia. 

Consecutive  go nc r; 1 1  infections  are  the  mbsl  frequenl  as  well  as  the 
most  important,  since  they  include  the  greal  majority  of  surgical 
and  obstetrical  septicemias  and  pyemias.  In  this  group  should  also 
be  included  certain  cases  in  which  the  primary  lesion  is  of  a  medical 
order,  to  wit,  occupying  such  parts  of  the  organism  as  to  render 
operative  intervention  impracticable.  This  evolution  is  met  with  not 
only  in  suppurative  lesions,  but  it  is  of  constant  occurrence  in  the 
course  of  the  most  varied  maladies.  For  instance,  when  an  erysip- 
elas or  a  pneumonia  terminates  in  death,  the  infection  nearly  always 
assumes  a  septicemic  form.  At  the  necropsy,  and  even  during  life, 
the  microbe  concerned,  be  it  the  streptococcus  or  the  pneumococcal 
is  found  in  all  the  organs  and  in  the  blood. 

The  same  evolution  may  be  observed  with  highly  differentiated 
bacteria.  Anthrax  is  a  good  illustration.  In  man,  the  bacillas  gives 
rise  to  a  local  lesion,  viz.,  a  malignant  pustule.  Too  often,  however, 
it  crosses  the  barrier  opposed,  to  it  by  the  organism  and  invades  the 
whole  system.  The  patient  is  then  said  to  have  died  from  anthrax 
septicemia.  It  may  happen,  at  least  in  animals,  that  even  the  local 
lesion  is  absent,  anthrax  manifesting  itself  as  a  true  septicemia. 

It  is  likewise  said  that  such  or  such  an  infection  assumes  a  septi- 
cemic form  in  cases  in  which  it  evolves  without  producing  its  usual 
manifestations  or  lesions.  Thus,  a  septicemic  form  of  typhoid  fever 
has  been  described.  It  would,  therefore,  be  easy  to  extend  the  limit 
of  septicemias  so  as  to  include  almost  all  infections,  at  least  certain 
forms  thereof.  To  avoid  the  confusion  which  would  result  from  such 
a  conception,  we  are  obliged  to  call  septicemias  those  bacteremias 
which  are  dependent  upon  common  microbes,  and  to  distinguish 
those  cases  in  which  a  well-defined  agent  has  from  the  first  or  con- 
secutively invaded  the  entire  organism  and  behaved  as  in  true  septi- 


248  TNFECTIO  US  DISEASES. 

eemia,  as  septicemic  forms  or  specific  septicemias.  Thus,  to  take 
the  examples  above  referred  to,  we  speak  of  a  streptococcic  septi- 
cemia and  a  staphylococcic  septicemia,  whereas,  if  the  question  is 
one  of  general  infection  by  the  bacillus  anthracis,  we  employ  the 
expressions  specific  septicemia  or  septicemic  form  of  anthrax.  By 
so  doing  we  conform  alike  to  clinical  data  and  to  the  results  of 
bacteriology. 

We  believed  it  proper  to  sharply  separate  consecutive  from  sec- 
ondary infections.  The  distinction  is  equally  based  upon  clinical 
experience  and  bacteriology.  In  consecutive  infections  it  is  the 
same  microbe  that  is  responsible  for  all  lesions.  Let  us  take,  for 
instance,  a  purulent  infection  consecutive  to  a  phlegmon :  clinicalty, 
it  is  the  same  process  that  has  become  generalized;  bacteriologically, 
it  is  the  same  microbe,  staphylococcus  or  streptococcus,  that  is  found 
both  in  the  initial  phlegmon  and  in  the  metastatic  abscesses.  Pyemia 
is  then  said  to  be  consecutive. 

On  the  other  hand,  let  us  take  a  case  of  diphtheritic  angina.  If 
the  patient  succumbs  to  septicemia,  as  the  latter  is  induced  by  the 
streptococcus  while  the  primary  agent  remains  localized  in  the  throat, 
we  say  that  this  septicemia  is  secondary.  It  is  a  second  process 
superadded  to  the  primary.  Likewise,  the  arthrites  of  gonorrhea  may 
be  produced  by  the  gonococcus.  This  is  an  instance  of  consecutive 
bacteremia  resulting  from  the  generalization  of  the  principal  infec- 
tion. In  other  cases  the  arthrites  are  clue  to  an  infection  superadded 
by  a  pyogenic  micro-organism  which  has  simply  profited  by  the 
urethral  lesion  and  invaded  the  economy:  this  is  a  secondary 
bacteremia. 

Bacteriology.  The  author  thought  it  well  to  include  septicemias 
and  pyemias  in  one  group.  While  pathological  anatomy  sharply 
separates  these  two  processes,  clinical  experience  recognizes  a  close 
relationship  between  them,  and  bacteriology  confirms  the  results  of 
observation  by  demonstrating  that  the  same  pathogenic  agents  are 
concerned  in  the  great  majority  of  cases. 

There  exist  certain  microbes  which  thus  far  have  been  met  with 
only  in  one  of  the  two  processes.  This  restriction,  while  preventing 
a  complete  identification  of  pyemias  and  septicemias  from  an  etio- 
logical standpoint,  is  not  of  sufficient  importance  to  separate  the 
two  morbid  groups.  The  most  common  agents  of  the  two  processes 
are,  in  fact,  streptococci  and  staphylococci,  less  frequently  the  other 
bacteria  to  which  reference  has  been  made  when  treating  of  suppu- 


SHl'TWHMIAS  AND  PYEMIAS. 


249 


ration,  and,  lastly,  in  some  cases,  more  or  lei    well-defined  microbe* 

or  even  simple  s:i.|  >roph yt es  thai  have  acquired  an  unexpected  < 

Of  virulence. 

The  same  agents  may  cause  septicemia  in  man  and  in  animals. 
In  the  latter,  however,  a  greal  number  of  speciei  have  been  mel  with 
which  thus  far  have  nol  been  detected  in  man.  Moreover,  il  i 
to  produce  in  animals  experimental  septicemias,  thi  tudy  ol  which 
has  largely  contributed  to  the  advance  of  bacteriology.  We  may, 
therefore,  divide  septicemias  into  two  greal  groups:  spontaneous  sep- 
ticemias— i.  e.,  those  occurring  withoul  any  voluntary  inoculation 
and  experimental  septicemias.  In  the  former  group  we  may  con- 
veniently study  the  septicemias  of  man,  affecting  exclusively  the 
human  species,  or  both  man  and  animals,  and  septicemias  attacking 
animals  only. 

Experimental  septicemias  may  also  be  subdivided  into  two 
groups,  according  as  (hey  are  produced  by  microbes  derived  from 
living  organisms  or  by  saprophytes  coming  from  putrefied  substances 
— air,  soil,  and  water. 

The  following  table  will  give  an  idea  of  the  principal  bacteria  thus 
far  encountered.  The  list  is  necessarily  incomplete,  but  its  main 
inconvenience  is  that  it  includes  identical  microbes  as  distant  species. 
In  fact,  it  is  known  how  difficult  it  is  to  determine  the  bacteria  met 
with.  Hence,  authors  have  often  held  as  new  such  microbes  as  have 
already  been  described,  but  the  biological  characters  of  which  have 
not  been  sufficiently  indicated  or  have  presented  variations  so  pro- 
nounced as  to  render  their  identification  a  matter  of  difficulty: 


Principal  Agents  of   Spontaneous   Septicemias. 


Of  Man  and  Sometime*  <>/  Animals. 
Streptococcus. 
Staphylococcus. 
Pneumococcus. 
Pneumobacillus. 
Proteus  hominis  capsulatus. 
Proteus  vulgaris. 
Proteus  septicus. 
Proteus  capsulatus  septicus. 
Bacillus  coli  communis. 
Bacillus  of  psittacosis. 
Bacillus  pyoevaneus. 
Micrococcus  tetragemis. 
Bacillus  of  false  anthrax. 
Bacillus  of  hemorrhagic  septicemia. 
Bacillus  septicus  putidus. 


Of  Animals. 

Bacillus  of  hemorrhagic  septicemia. 

Chicken  cholera. 

Disease  of  pigeons. 

Disease  of  canaries. 

Cholera  of  ducks. 

Infectious  enteritis  of  chickens. 

Septicemia  of  rabbits. 

Purulent  rhinitis  of  rabbits. 

Septicemia  of  ferrets. 

Disease  of  wild  animals. 

Septic  pleuropneumonia  of  calves. 

Contagious  pneumonia  of  pigs. 

Infectious  pneumoenteritis. 

B.  of  septicemia  of  rats. 

B.  capsulatus. 

B.  hydrophilus  fuscus. 


250  IXFECTIO  US  DISEASES. 

Experimental   Septicemia. 

Of  Animal  Origin.  Of  Saprophytic  Origin. 

Agents  of  septicemias  of  salivary  or  Septicemia  of  Coze  and  Feltz. 

nasal  origin:  Septicemia  of  Davaine. 

Bacillus  salivarius  septicus.  Experimental  septicemia  of  mice. 

Micrococcus  salivarius  septicus.  Experimental  septicemia  of  rabbits. 

B.  crassus  sputigenus.  Bacillus  septicus  agrigenus. 

B.  smaragdinus  fetidus.  B.  canilicolis  brevis. 

B.  salivarius  canis. 
Agents   of  sejDticemias  of  intestinal 
origin: 

B.  cavicida  havaniensis. 

B.  caniculicida  havaniensis. 

B.  acidiformans. 

B.  leparis  lethalis. 

Streptococcus. 

The  agents  of  pyemia  are  far  less  numerous.  The  principal  ones 
are  the  streptococcus  and  staphylococcus,  to  which  may  be  added  a 
special  bacillus  described  by  Levy. 

Certain  more  highly  organized  parasites  may  be  classified  with  the 
agents  of  pyemia:  actinomycetes,  for  example,  which  induce  even  in 
man  multiple  suppurations,  and  thus  give  rise  to  a  true  chronic 
pyemia.  The  oospora  farcinosa  and  oidium  albicans  are  capable 
of  acting  in  a  similar  manner.  These  various  pyemias,  however, 
should  be  considered  as  specific  pyemias.  The  common  pyemias  are 
almost  always  dependent,  in  animals  as  well  as  in  man,  upon  the 
habitual  agents  of  suppuration — streptococci  and  staphylococci. 

Experimental  Septicemias  and  Pyemias. 

The  study  of  septicemias  and  pyemias  which  may  experimentally 
be  produced  in  animals  is  of  great  importance  in  medicine,  since  it 
has  powerfully  served  to  establish  the  fundamental  principles  of 
bacteriology  on  solid  bases.  These  experimental  maladies  may  very 
readily  be  produced;  it  suffices  to  inject  into  animals  saliva  or  fecal 
matters,  to  inoculate  putrefied  substances,  or  contaminated  water, 
or  to  introduce  dust  beneath  their  skin.  Many  experimenters  eagerly 
entered  this  field  of  research  and  described  a  great  number  of  experi- 
mental diseases  characterized  by  septicemic  manifestations. 

Researches  of  this  kind  are,  at  present,  rather  neglected;  it  would 
be  of  value,  however,  to  pursue  such  investigations  in  order  to 
demonstrate  what  relationship  exists  between  diseases  caused  by 
saprophytes  swarming  in  putrid  matters  or  found  in  the  air,  soil,  and 
water,  and  spontaneous  diseases,  developing  without  any  experimen- 


SEPTICEMIAS  AND  PYEMIAS.  251 

tal  influence,     Important  data  may  thus  be  obtained  regarding  the 
distribution  of  pathogenic  agents  outside  living  being    and  the  i  o 
sible  sources  of  contamination. 

History.  We  shall  not  dwell  upon  the  work*  of  the  pre-bacterial 
period ;  a  very  full  account  of  them  \\  ill  he  Ion  ml  in  tli''  highly  inter- 
esting article  of  .Icnimel.1  li  will  suffice  to  recall  thai  Gaspard  wae 
the  first  to  undertake  experimental  researches  upon  purulenl  and 
putrid  infections.2  The  results  were  verified  by  Magendie  (1824 
Trousseau  and  Dupuy  (1826),  Leurel  (1826),  Boyer  (1834),  etc.  In 
a  remarkable  work  d'Arcel  demonstrated  thai  putrid  serosities  give 
rise  to  putrid  infections  without  abscess;  thai  flic  injections  of  pus 
generally  cause  death  without  lesions  (1842).  The  pathogenic  idea 
of  d'Arcet  was  developed  by  Virchowand  accepted  by  many  authors; 
pyemia  was  considered  as  a  septicemia  complicated  with  embolic 
migrations.  In  18S9  Verneuil  stated  thai  pyemia  is  an  embolic 
septicemia  and  that  purulenl  infect  ion  is  a  termination  of  septicemia. 

The  researches  of  Berard,  Oastelneau,  Ducret,  Sedillot,  Batailhe, 
•Gamgee,  Chauveau,  Billroth,  and  0.  AA'eber  established  experimen- 
tally that  putrefied  pus  induces  septicemia  without  abscesses,  while 
fresh  pus  gives  rise  to  septicemia  or  pyemia — a  septicemia  when  a 
great  amount  of  pus  is  at  once  introduced;  a  pyemia  when  small 
doses  are  injected  and  the  inoculations  are  repeated  several  days 
in  succession.  The  possibility  of  reproducing  in  animals  the  two 
infectious  processes  which  were  known  to  clinical  experience  led 
naturally  to  investigation  of  the  mechanism  of  the  events.  A  few- 
authors  believed  that  pus  was  engendered  by  the  white  corpuscles  : 
such  was  the  opinion  of  Sedillot,  Billroth,  and  0.  Weber. 

In  order,  however,  to  explain  the  general  phenomena  and  the  mode 
of  development  of  septicemias,  another  factor  was  to  be  taken  into 
account.  This  factor  was  first  looked  for  in  chemical  substances. 
The  toxic  theory,  which  contains  a  great  deal  of  truth,  was  further 
developed  by  the  works  of  Panum.  It  is  well  demonstrated,  in  fact, 
that  the  symptoms  observed  in  infections  depend  upon  toxic  sub- 
stances ;  but  by  what  mechanism  are  the  latter  produced?  Pasteur's 
works,  by  showing  the  animate  nature  of  fermentations,  led  to  a 
search  among  the  infinitely  small  for  the  cause  or,  at  least,  the  start- 

1  Jeannel.  Art.  Septicemic  et  pyoh&nie.  Encyclopedic  intemationale  de  chirurgie, 
1883,  t.  i.  p.  311. 

2  Gaspard.  Memoire  physiologique  sur  les  maladies  purulentes  et  pumdes  et  sur  la 
vaccine.     Journal  de  Magendie.  1S'2'2.  p.  1:   1S24.  p.  1. 


252  INFECTIOUS  DISEASES. 

ing  point  of  the  events.  Thus  we  arrive  at  the  second  or  microbic 
period  of  the  history  of  septicemias. 

From  1S65  to  1S69  Coze  and  Feltz1  published  a  scries  of  researches 
on  septicemia.  They  succeeded  in  inducing  septicemic  conditions 
by  various  procedures.  Sometimes  they  introduced  putrid  sub- 
stances beneath  the  skin  of  clogs  and  rabbits;  in  other  cases,  they 
introduced  blood  derived  from  typhoid  fever,  variola,  puerperal  fever, 
or  scarlatina  patients.  In  all  instances  the  animals  died,  and  the 
necropsy  revealed  in  the  blood  a  great  number  of  microbes,  bacilli, 
cocci,  and  little  chains.  These  authors  must  be  credited  with  having 
( leveloped  a  fertile  method  of  experimentation  and  having  observed 
an  important  result,  to  wit,  the  increase  of  virulence  when  inocula- 
tions in  series  are  made  upon  animals.  This  result  was  shown  to  be 
verified  by  Davaine,2  who  left  cow's  blood  to  putrefy  for  ten  days  in 
the  month  of  July,  and  injected  from  two  to  fifteen  drops  of  it  into 
rabbits,  with  a  fatal  result.  By  making  successive  inoculations,. 
Davaine  recognized  that  on  the  twenty-fifth  passage  the  blood  was 
virulent  in  a  dose  of  one-trillionth  of  a  drop  or  at  times  even  one 
ten-trillionth  of  a  drop  (0.000,000,000.05  to  0.000,000,000,005  c.cm.). 
He  concluded  that  septicemia  is  a  putrefaction  effected  in  the  blood 
of  a  living  animal  by  the  activity  of  vibrios. 

These  results  aroused  doubt  and  criticism.  Bouley,  Arulpian,  who 
had  at  first  been  skeptical,  repeated  Davaine's  experiments,  and 
Behbier,  as  well  as  Liouville  and  Colin,  recognized  their  exactness. 

The  next  attempt  was  made  with  the  view  of  discovering  the 
characters  of  the  agents  capable  of  causing  such  accidents.  Popoff3 
made  a  first  attempt  by  injecting  into  rabbits  the  yeast  of  beer  and 
a  micro-organism  cultivated  in  the  urine.  Klebs  produced  septi- 
cemias by  injecting  cultures  of  putrefied  tissue.  Koch,4  however, 
should  be  credited  with  the  first  efforts  to  characterize  and  specify 
the  various  experimental  infections.  This  work,  which  is  very 
remarkable  for  the  epoch  at  which  it  appeared,  does  not  give  suffi- 
cient information  as  to  the  characters  of  the  pathogenic  agents,  so 

1  Coze  and  Feltz.  Recherches  exp.  sur  la  presence  des  infusoires  et  l'etat  du  sang 
dans  les  maladies  infectieuses.     Strasbourg,  1866-69. 

2  Davaine.  Recherches  sur  la  septicemic  et  sur  les  caracteres  qui  la  dissingue  de  la 
maladie  charbonneuse.  Comptes  R.  Acad,  des  Sciences,  Jan.  25,  1869.  Recherches  sur 
quelques  questions  relatives  a  la  septicemic     Acad,  de  M6decine,  September  17,  1872. 

3  Popoff.  Untersuchungen  iiber  die  Wirkungen  der  Bierhefe  und  der  in  der  Pas- 
teurschen  Flussigheit  enthaltenen  Organismen  auf  der  thierischen  Korper.  Berlin, 
med.  Wochenschrift,  1872. 

4  Koch.     Ueber  die  Aetiologie  der  Wundinfectionskrankheiten.     Leipzig,  1876. 


SEPTICEMIAS  AND  PTEMIAS. 

that,  with  regard  to  several  of  th<  m,  it  i  difficull  to  determine  their 
relationship  with  the  agents  of  other  experimental  diseasei  and  with 
those  of  spontaneous  infections. 

Septicemias  of  Salivary  Origin.  Hitherto  experimental  septice- 
mias were  produced  by  injections  of  putrefied  sub  tanc<  or  patho- 
logical products.  The  inoculation  of  normal  organic  fluids,  however, 
may  produce  the  same  results.  In  1881  Pasteur  obtained  a  septi- 
cemia in  the  rabbit  by  inoculating  the  saliva  of  a  boy  the  victim 
of  hydrophobia.  Sternberg  arrived  a1  the  same  resull  by  injecting 
the  saliva  of  a  healthy  man;  he  carefully  studied  the  characters  of 
this  agent,  and  Fraenkel  demonstrated  its  identity  with  the  pneumo- 
coccus. 

At  the  present  lime  septicemias  have  been  well  studied  and  classi- 
fied.   We  shall  briefly  indicate  the  characters  of  the  principal  ' 

The  inoculation  of  the  saliva  may  give  rise  to  several  lorn. 
septicemias  in  animals.  The  salivary  septicemia  with  pneumococcus 
is  obtained  by  inoculating  the  rabbit  or,  better,  the  mouse.  The 
animal  succumbs  in  twenty-four  or  forty-eight  hours  and  the  necropsy 
reveals  the  easily  recognizable  encapsulated  microbe  in  the  blood  and 
organs. 

The  B.  crassus  sputigenus  of  Kreibohrn1  is  an  encapsulated  bacillus 
analogous  to  if  not  identical  with  the  pneumobacillus  of  Fried- 
laender;  it  differs  from  it  only  in  that  it  is  not  decolorized  by  Gram's 
method.     It  kills  mice  and  rabbits  within  twenty-four  hours. 

The  B.  tenuis  sputigenus2  is  an  encapsulated  bacillus,  smaller  than 
the  preceding  one,  is  stained  by  Gram's  method  and  readily  develops 
in  the  various  culture  media.  It  is  pathogenic  for  the  rabbit  and 
white  rat,  but  not  for  the  guinea-pig  and  white  mouse. 

Aside  from  these  septicemias  produced  by  the  human  saliva,  there 
is  one  which  Fiocca  caused  with  the  saliva  of  dogs  and  cats.  It  is 
due  to  a  small  bacillus,  which  in  cultures  on  potatoes  resemble-  a 
micrococcus.  It  is  a  facultative  anaerobic  and  does  not  liquefy 
gelatin.  The  cultures  are  pathogenic  for  rabbits,  guinea-pigs,  young 
rats,  and  mice. 

Septicemias  of  Nasal  Origin.  Of  the  septicemias  of  nasal  origin, 
we  must  mention  that  which  Reimann3  has  produced  with  a  bacillus 
found  in  a  case  of  ozena:  the  B.  smaragdinus  fctidus.    It  is  a  facul- 

1  Fliigge.    Die  Mikroorganismen.     Leipzig,  1SS6,  p.  2(30. 

2  P;msim.    Bakteriologisohe  Studien  des  Auswurfs.  Virchow's  Archiv,  Bd.  exxii    li 

3  Reimann.     Inaug.  Diss.,  Wiirzburg.  1SS7. 


254  INFECTIOUS  DISEASES. 

tative  anaerobic.  Its  intravenous  or  subcutaneous  inoculation  kills 
rabbits  in  thirty-six  or  forty-eight  hours;  the  necropsy  reveals  sub- 
pericardiac  and  subpleural  hemorrhages.  Large  numbers  of  bacilli 
are  seen  in  the  blood  and  organs. 

Septicemias  of  Intestinal  Origin.  The  genuine  microbe  of  septi- 
cemias of  intestinal  origin  is  the  colon  bacillus.  A  great  number  of 
infections  attributed  to  other  agents  must  be  looked  upon  as  due  to 
varieties  of  this  microbe,  viz.,  to  varieties  of  B.  coli  communis  and 
B.  lactis  aerogenes. 

The  B.  cavicida  havaniensis  (Sternberg),  found  in  the  intestine  of 
a  subject  dead  from  yellow  fever,  seems  to  be  no  more  than  a  variety 
of  B.  coli.  It  exerts  no  action  upon  rabbits  and  kills  guinea-pigs 
within  ten  or  twelve  hours.  On  the  contrary,  the  B.  cuniculicida 
havaniensis  (Sternberg),  obtained  under  the  same  circumstances,  is 
a  variety  of  colon  bacillus  which,  as  its  name  indicates,  is  pathogenic 
for  the  rabbit. 

The  B.  acidiformans  (Sternberg),  derived  from  the  liver  of  various 
cadavers,  seems  to  the  author  to  be  analogous  to  the  B.  lactis 
aerogenes.     It  Mils  rabbits  and  guinea-pigs  in  twenty-four  hours. 

Septicemias  and  Pyemias  of  Saprophytic  Origin.  As  has  already 
been  stated,  Koch  had  described  several  infections  consecutive  to 
inoculations  of  putrefied  substances.  There  is,  in  the  first  place,  the 
septicemia  of  mice,  caused  by  the  injection  of  putrefied  blood.  This 
affection,  which  is  due  to  a  small  bacillus  measuring  \fi  by  0.1/^-, 
attacks  only  the  house  mouse,  not  the  field  mouse  or  rat.  By  inject- 
ing into  rabbits  an  infusion  of  putrefied  meat,  Koch  produced  a  new 
septicemia,  the  septicemia  of  rabbits,  due  to  microbes  0.8//  to  lft  in 
length.  Gaffky  observed  a  similar  septicemia  by  injecting  the 
water  of  Panke  into  rabbits.  The  belief  is  now  gaining  ground  that 
all  these  affections  depend  upon  the  same  microbe  as  that  of  chicken 
cholera. 

Sewer  water  and  the  soil  contain  a  certain  number  of  septicemic 
agents,  amongj which  are  the  B.  canalicolis  brevis  and  the  B.  septicus 
agrigenus.  The  former  was  found  by  Mori  in  the  sewrer  water  of 
Berlin;  it  is  pathogenic  for  mice,  rabbits,  and  guinea-pigs,  but  not 
for  pigeons.  The  latter  microbe,  discovered  by  Nicolaier  in  manured 
fields,  resembles  the  bacillus  of  chicken  cholera,  but  is  a  trifle  longer. 
When  inoculated  into  the  veins  it  kills  rabbits  in  twenty-four  or 
thirty-six  hours.     It  is  also  pathogenic  for  mice. 

To  sum  up,  the  great  majority  of  diseases  experimentally  produced 


SEPTICEMIAS  AND  PTEMIAS. 

are  due  to  microbes  which  we  find  in  natural  di  ea  e  .  [nm< 
the  same  microbes  under  differenl  names  are  encountered,  notably 
the  streptococcus,  pneumococcus,  pneumobacillus,  and  colon  bacillus. 
Let  us  add  the  proteus  vulgaris,  tnirabilis,  and  Zenkeri,  which  are 
so  frequently  present  in  decaying  matters  and  the  cultures  of  which 
give  rise  to  septicemias  in  animals, 

Spontaneous  Septicemias  and  Pyemias  of  Animals. 

Hemorrhagic  Septicemias.     There  exists  a  group  of  micr< 
designated  as  bacilli  of  hemorrhagic  septicemias,  the  importance  of 

which  is  far  greater  than  was  at  first  believed.  Hie  type  of  the  kind 
is  represented  by  the  bacillus  of  chicken  cholera.  It  wassoon  Learned 
that  the  microbes  of  experimental  septicemia  produced  by  Koch  and 
Gaffky  were  no  other  than  the  bacillus  of  chicken  cholera.  It 
later  recognized  that  a  great  number  of  affections  observed  in  bird-, 
cows,  wild  animals,  and  the  hog  depend  upon  microbes  analogous  to 
or  identical  with  the  bacillus  of  chicken  cholera.  The  presen< 
this  agent  in  putrefied  substances  (Koch)  or  contaminated  water 
(Gaffky)  shows  how  widely  it  is  distributed  and  explains  the  appa- 
rently spontaneous  development  of  certain  epizooties. 

The  bacillus  of  hemorrhagic  septicemia  is  the  agent  of  at  least 
fifteen  diseases  that  were  once  held  to  be  different.  In  some  recent 
contributions,  Dr.  Lignieres  introduces  other  affections,  notably  the 
diseases  of  dogs  and  cats  and  the  typhoid  malady  of  horses,  and  pro- 
poses to  call  the  group  pasteurelloses.  Distinctions  may  be  estab- 
lished according  to  the  species  spontaneously  affected  and  those  which 
may  be  infected  in  laboratories.  It  is  to  be  noted,  however,  that 
the  pathogenic  action  varies  considerably  with  the  origin  of  the  virus. 
For  instance,  rabbits  and  chickens,  which  are  so  sensitive  to  chicken 
cholera,  are  refractory  to  the  other  morbid  varieties:  while,  on  the 
other  hand,  the  guinea-pig,  so  slightly  susceptible  to  chicken  cholera, 
may  easily  contract  other  forms  of  the  infection. 

It  may, therefore, be  questioned  whether  affections  so  clearly  differ- 
ing from  each  other  can  be  classed  in  one  morbid  group.  They  have 
been  grouped  for  the  reason  that  the  pathogenic  agents  found  in 
these  diverse  diseases  possess  analogous  or  identical  morphological 
and  biological  characters.  Morphologically,  they  are  small,  ovoid 
bacilli  measuring  l/i  by  0.25/*,  and  assume,  in  certain  media,  the 
aspect  of  micrococci  or  diplococci.    They  are.  with  few  exceptions, 


256  INFECTIOUS  DISEASES. 

non-motile.  None  is  spore-bearing.  Certain  species,  like  that  of 
chicken  cholera,  cannot  develop  without  oxygen;  most  of  the  other 
varieties  arc  facultative  anaerobics. 

The  differences  existing  between  the  various  agents  of  hemorrhagic 
septicemia  recall  those  observable  in  the  group  of  colon  bacilli.  The 
comparison  is  the  more  interesting  as  the  characters,  considered  as 
distinctive,  are  the  same  in  both  instances.  These  consist  in  the 
different  appearances  of  the  cultures  on  potato  and  in  milk,  the 
production  of  indol,  and  motility  and  non-motility  of  the  elements. 
All  these  characters,  however,  are  contingent  and  variable  and  do 
not  suffice  to  specify  a  microbe.  The  same  is  true  as  regards  the 
pathogenic  action.  The  microbe  of  chicken  cholera  is  extremely 
virulent  for  the  chicken  and  for  the  rabbit,  while  it  is  slightly  so  for 
the  guinea-pig;  its  inoculation  produces  nothing  more  than  an 
abscess  in  man,  the  horse,  and  sheep. 

Such  are  the  reasons  which,  since  the  works  of  Hueppe,1  Baum- 
garten,2  Caneva,3  and  Bunzl  Federn4  have  led  to  the  creation  of  the 
group  of  hemorrhagic  septicemias.  We  should  like  to  include  in  this 
group  the  epizootic  purulent  rhinitis  of  the  rabbit.5  This  affection, 
of  not  uncommon  occurrence,  attacked  some  of  the  rabbits  of  our 
laboratory  in  the  spring  of  1900.  We  then  seized  the  opportunity 
to  take  up  the  study  of  this  malady.6 

Epizootic  Purulent  Rhinitis  of  Rabbits.  The  purulent  rhinitis 
starts  with  an  abundant  nasal  discharge.  The  animal  grows  thin  and 
loses  appetite.  The  discharge  lasts  about  a  week  without  any  other 
symptoms,  and  the  affection  invariably  ends  in  death.  In  one  case, 
fatal  termination  seemed  to  be  hastened  by  profuse  nasal  hemor- 
rhages. At  the  necropsy  upon  these  rabbits,  the  mucous  membrane 
of  the  nasal  fossa?  is  found  to  be  the  seat  of  congestion ;  the  trachea, 
bronchi,  and  sinuses  of  the  face  contain  a  clear,  slightly  purulent 
mucus,  and  one  is  at  times  surprised  at  the  absence  of  other  micro- 

1  Hueppe.  Ueber  die  Wildseuche  und  ihre  Bedeutung  fur  Nationalokonomie  und 
Hygiene.     Berl.  klinische  Wochenschrift,  18S6,  p.  753. 

2  Baumgarten.     Lehrbuch  der  pathologischen  Mykologie,  1890,  p.  489. 

3  Caneva.  Ueber  die  Bakterien  der  hamorrhagischen  Septikamie.  Centralb.  f.  Bak- 
teriologie,  1891,  Bd.  ix.,  p.  557. 

4  Bunzl  Federn.  Bemerkungen  iiber  Wild  und  Schweineseuche.  Ibid.,  p.  787.  Unter- 
suehungen  iiber  einige  Erkrankungen  des  Schweine.     Archiv  f.  Hygiene,  1891. 

5  There  is  a  very  interesting  study  on  hemorrhagic  septicemia  in  the  book  of  Nocard 
and  Leclainche.     Les  maladies  microbiennes  des  animaux,  Paris,  1896. 

8  Roger  and  Weil.  Recherches  bacteriologiques  sur  la  rhinite  purulente  epizootique 
des  lapins.     Arch,  de  m4d.  exp.,  July,  1901. 


SEPTICEMIAS  AND  PTEMIA8.  257 

scopic  lesions.     In  certain  cases,  however,  there  is  a  marked    pleni- 
zation  in  the  lungs,  even  hemorrhagei  ;  bh<  o  of  the  abdominal 

cavity  are  congested,  and  the  spleen  enlarged.  The  pathogenic 
agent,  examined  in  the  pus  or  in  cultures,  appear  in  the  form  of 
oval  elements  which  might  easily  be  taken  for  micrococci.  The} 
small,  non-motile  bacilli  measuring  on  an  average  0.6//  to  0.7//, 
sometimes  \/>.  They  are  stained  with  difficulty  and  are  decolorized 
by  Gram's  method.  Strictly  aerobic,  this  microbe  rapidly  develops 
in  ox  serum  gelatin.  Us  vitality  and  virulence  are  well  preserved 
only  in  the  serum  of  rabbits.  Cultures  made  in  this  medium  were 
employed  in  our  experiments  and  enabled  us  to  produce  in  rabbits 
a  disease  analogous  to  the  spontaneous  affection  by  its  evolution  and 
lesions. 

This  disease  of  the  rabbit  lias  been  the  object  of  two  publications 
in  Germany.  The  first  by  dale  is  that  of  Beck,  who  isolated  a 
pathogenic  bacillus  comparable  to  that  of  human  influenza.  Krauss 
found  a  bacillus  which  he  believed  represented  a  new  species.  Our 
bacillus  is  not  identical  with  the  two  preceding  ones.  Neverthe 
it  is  quite  likely  that  it  is  the  same  parasite  assuming  somewhat 
peculiar  characters  according  to  various  epizooties. 

Human  Septicemias  and  Pyemias. 

The  preliminary  study  above  presented  on  experimental  and  spon- 
taneous septicemias  and  pyemias  of  animals  will  facilitate  compre- 
hension of  these  infections  in  man. 

Many  pathologists  divide  septicopyemias  into  surgical,  puerperal, 
and  medical.  It  seems  to  me  more  rational  to  take  into  account 
both  their  point  of  departure  and  nature.  We  shall  first  study 
primary,  traumatic,  and  mitogenetic  septicemias.  They  may  be- 
come manifest  at  once  without  any  appreciable  cause  or  in  conse- 
quence of  a  traumatism  or  important  surgical  operation.  Dr.  Jayle 
has  well  demonstrated  that  a  great  number  of  cases  considered  as 
instances  of  shock  consecutive  to. opening  the  abdomen  must  be 
attributed  to  acute  septicemia,  commonly  due  to  streptococci.  A 
second  group  includes  septicemias  consecutive  to  a  local  lesion.  If 
the  latter  is  created  by  a  highly  differentiated  micro-organism,  the 
septicemia  is  said  to  be  specific  and  will  not  be  dealt  with  here.  We 
are  to  study  only  those  cases  in  which  the  lesion  and  its  consequences 
depend  upon  common  bacteria,  generally  of  the  pyogenic  group. 

Finally,  secondary  septicopyemias  are  those  in  which  the  general 


258  INFECTIOUS  DISEASES. 

infection  is  induced  by  an  ordinary  microbe  secondarily  engrafted 
upon  a  previous  microbic  lesion. 

Bacteriology.  The  microbes  commonly  found  in  human  septi- 
cemias and  pyemias  are  already  known  to  us:  they  are  chiefly  the 
streptococci,"  staphylococci,  pneumococci,  pneumobacilli,  proteus  and 
colon  bacilli.     (See  table,  p.  249.) 

Differentiation  of  the  various  microbes  found  in  septicemias  from 
the  pneumobacillus  of  Friedlaender  has  been  based  upon  the  results 
of  inoculations.  In  fact,  it  is  admitted  that  the  pneumobacillus  is 
not  pathogenic  for  the  rabbit.  The  author's1  researches,  however, 
demonstrate  that  its  intravenous  inoculation  gives  rise  to  a  fatal 
septicemia  characterized,  in  a  great  number  of  cases,  by  multiple 
hemorrhages.  This  fact,  which  is  contrary  to  classical  opinion,  must, 
I  think,  be  emphatically  stated.  As  a  result  of  intravenous  inocu- 
lations, there  may  be  observed  one  of  the  following  three  types : 

1.  Hemorrhagic  septicemia  with  swelling  and  infarction  of  Peyer's 
patches,  intestinal  hemorrhages. 

2.  Septicemia,  without  any  obvious  lesions,  with  numerous  mi- 
crobes in  the  organs  and  the  blood,  or  only  in  the  organs — i.  e., 
without  microbes  in  the  blood,  at  least  so  far  as  microscopic  exam- 
ination reveals. 

3.  A  chronic  disease  characterized  by  albuminuria  associated  with 
renal  alterations;  at  times  by  cardiac  dilatations  and  paralyses. 

These  results  seem  to  authorize  us  to  more  closely  ally  the  pneu- 
mobacillus with  various  encapsulated  microbes  pathogenic  for  the 
rabbit.  The  manifestations  observed  are  also  interesting,  because 
they  resemble  those  encountered  in  man  and  serve  to  elucidate  their 
mechanism. 

The  colon  bacillus  is  very  frequently  concerned  in  septicemia.  The 
microbe  of  psittacosis,  which  does  not  differ  greatly  from  this,  may 
be  considered  as  a  species  intermedial  between  the  colon  bacillus 
and  the  bacillus  of  Eberth.  It  was  discovered  by  Nocard  in  diseased 
parrots,  and  has  been  well  studied  by  Gilbert  and  Fournier.  These 
authors  have  observed  an  epidemic  attacking  five  individuals  in  one 
family.  Three  were  slightly  affected;  the  two  others  succumbed  in 
eight  or  nine  days.  The  microbe  was  detected  at  the  necropsy  in 
the  blood  of  the  heart,  and  proved  to  be  extremely  virulent  for  par- 
rots, mice,  guinea-pigs,  rabbits,  and  pigeons.    Psittacosis  manifests 

1  Roger.  Action  du  bacille  cle  Friedlaender  sur  le  lapin.  Soc.  de  biologie,  January  20, 
1894. 


SEPTICEMIAS  AND  PYEMIAS,  260 

itself  in  man  by  symptoms  resembling  those  of  adynamic  pneumo 
of  typhoid  fever,  with  pronounced  predominance  of  aervou    pertur- 
bations.1 

Although  unable  to  affirm  posil  ively  it  pathogenic  rdle,  we  hould 
like  to  aote  that  the  leptothrix  buccalis  ha  al  time  invaded  the 
viscera.  Poncel  reports  the  observation  of  a  patienl  who  succumbed 
to  a  putrid  infection  consecutive  to  a  dental  abscess.  Quantities  of 
this  microbe  were  found  in  the  metastatic  foci  and  cardiac  coagula. 

Reference  has  already  been  made  to  the  numerous  investigations 
willi  regard  to  hemorrhagic  septicemias  of  animals.  No  less  impor- 
tant researches  luive  been  pursued  with  regard  to  hemorrhagic  sep- 
ticemias of  man.  II  will  si  ill  ice  to  mention  those  of  Klebs,  I  feci,  W. 
(-Iicyiie,  Petrone,  Let/.erich,  Dennne,  and  Illava.  The  last-named 
author  has  even  advanced  the  idea  thai  hemorrhagic  fevers  are  due 
to  a  superadded  infection  by  a  heinorrhagiparous  bacterium.  This 
opinion  will  receive  notice  Later  in  connection  with  variola.  In  cer- 
tain cases  of  hemorrhagic  infection  there  has  been  found  a  bacillus 
analogous  to  that  of  chicken  cholera  or  rabbit  septicemia.  Tizzoni 
and  Giovannini,  Babes,  and  Kolb  have  found  a  similar  microbe  in 
purpura  hemorrhagica.  Babes  further  asserts  thai  this  microbe  is 
present  in  the  most  varied  infections — septic  pneumonia,  omphalitis, 
keratitis,  followed  by  hemorrhagic  septicemia,  hemorrhagic  variola, 
and  septicemia  resembling  typhus  fever.  Belfanti  and  Pescarodo 
have  found  the  same  microbe  in  a  case  of  tetanus.  Sternberg  has 
encountered  it  in  the  liver  of  an  individual  dead  from  yellow  fever. 
Lastly,  we  have  found  in  a  case  of  putrid  pleurisy  an  analogous 
microbe,  present  in  the  exudate  with  various  other  bacteria — viz.. 
streptococcus,  staphylococcus,  and  colon  bacillus.  It  was  the  typical 
aerobic,  ovoid  bacterium  developing  in  agar-agar  and  gelatin,  like  the 
microbe  of  chicken  cholera.  Its  subcutaneous  inoculation,  even  in 
very  small  doses,  produced  in  the  rabbit  a  septicemia  ending  in  death 
within  twenty-four  hours,  while  in  the  guinea-pig  there  appeared  at 
the  point  of  inoculation  a  profuse  serous  exudation,  then  an  abscess 
which  opened  in  a  few  days  and  healed  spontaneously.  It  is  evi- 
dently difficult  to  say  what  r61e  had  been  played  by  this  microbe  in 
the  genesis  of  the  symptoms  presented  by  the  patient;  it  is  never- 
theless interesting  to  call  attention  to  the  rare  observations  in  which 
the  bacillus  of  hemorrhagic  septicemia  has  been  noticed  in  man. 

1  Gilbert  and  Fournier.    Contribution  a  1  etude  de  la  psittacose.    Aeademie  de  m^de- 
dne  (report  by  Dr.  Debove),  October  20,  IS96. 


260  INFECTIOUS  DISEASES. 

If  we  further  bear  in  mind  that  the  microbe  of  hemorrhagic  septi- 
cemia may  be  encountered  as  a  simple  saprophyte  in  the  buccal 
cavity  of  man  (Baumgarten),  dog,  and  cat  (Smith),  we  shall  conclude 
that  the  microbes  constituting  this  group  must  play  in  human  path- 
ology a  role  of  greater  consequence  that  was  at  first  believed. 

Relative  Frequency  of  the  Various  Septic  and  Pyemic  Agents. 
Having  briefly  reviewed  the  principal  microbes  which  may  be  found 
in  cases  of  bacteremia,  we  must  determine  the  relative  frequency  of 
each  of  them.  The  most  complete  study  on  this  subject  is  that  of 
Canon,1  whose  investigations  covered  seventy  cases.  The  author 
divides  his  results  into  three  categories,  according  as  the  process 
was  one  of  septicemia,  septicopyemia,  or  true  pyemia — i.  e.,  pyemia 
without  the  presence  of  microbes  in  the  blood. 

In  the  cases  of  septicemia,  twenty  in  number,  Canon  has  found 
chiefly  the  streptococcus,  less  frequently  the  staphylococcus,  once 
the  pneumococcus,  at  another  time  the  colon  bacillus,  and,  lastly, 
in  one  case,  an  unidentified  bacillus.  These  microbes  were  found  in 
the  blood  and  in  the  primary  focus.  In  two  cases,  however,  the 
initial  lesion  contained  both  the  streptococcus  and  staphylococcus, 
but  the  latter  alone  entered  the  blood.  These  results  were  secured 
■with  blood  obtained  from  the  cadaver.  Examinations  made  seven 
times  upon  the  living  subject  gave  positive  results  in  three  in- 
stances. 

The  second  group  comprises  twenty  cases  of  bacteremia  with 
metastatic  foci.  In  eleven  patients  with  various  primary  lesions 
Canon  found  mainly  streptococci  and  staphylococci,  once  the  pneu- 
mococcus, at  another  time  a  large  unidentified  bacillus.  Out  of  five 
examinations  of  the  blood  made  during  life,  four  yielded  positive 
results. 

The  author  next  reports  five  cases  of  osteomyelitis.  With  the 
majority  of  German  physicians  he  interprets  this  affection  as  a 
pyemia  of  the  developmental  period.  It  is  rather  a  staphylopyemia, 
since  out  of  the  five  cases  the  aureus  was  found  three  times,  once 
the  albus,  and  once  a  diplococcus.  Examination  of  the  blood 
during  life  gave  positive  results  four  times.  In  a  last  group  the 
report  concerns  cholelithiasis ;  the  pneumococcus  and  staphylococcus 
were  found. 

1  Canon.  Zur  Aetiologie  der  Sepsie,  Pyamie  unci  Osteomyelites  auf  Grund  bakte- 
riologischer  TJntersuchungen  des  Blutes.  Deutsche  Zeitschrift  f.  Chirurgie,  1894,  Bd. 
xxxvii. 


SEPTICEMIAS  AND  PYEMIAS.  261 

Finally,  there  remain  those  case    in  which  tneta  tatic  foci 
developed  without  any  microbes  being  found  in  the  blood.    There 
are  cases  of  pure  pyemia  upon  which  Canon  doe*  nol  dwell. 

IViniKcliky'  has  :i.lso  examined  59  ca  e    and  Sittmann  23  ca 
From  these  researches  it  is  seen  thai  the  microbe    mo  I  frequently 
encountered  in  bacteremia  are  the  streptococcus  and    taphylococcus, 
next  comes  pneumococcus,  and  then  colon  bacilli]  , 

Clinical  Evolution.    We  do  not  intend  to  describe  the    ymptoms 
and  lesions  of  bacteremias;  we  shall  confine  our  remarks  to  a 
general  considerations,  the  clinical  history  of  these  infections  having 
long  since  been  known. 

Bacteremias  may  occur  under  two  quite  distincl  conditions. 
Sometimes  (here  is  a  wound  or  a  previous  :i Iteration;  sometimes  the 
organism  is,  or  appears  to  be,  normal.  The  first  group  includes 
puerperal,  surgical,  and  certain  medical  bacteremias,  notably  those 
arising  in  the  course  or  in  consequence  of  eruptive  fevers,  anginas. 
and  tuberculosis.  The  second  group  comprises  those  cases  in  which 
infection  may  be  considered  spontaneous  or  cryptogenetic.  Puer]  teral 
infections  are  most  frequently  caused  by  the  streptococcus.  Accord- 
ing to  Morse,  this  micro-organism  is  found  in  67  per  cent,  of  the  c. 
The  possibility  of  infection  by  the  staphylococcus  aureus  and  even 
by  the  gonococcus  has  also  been  demonstrated. 

The  fact  that  the  streptococcus  is  so  frequently  concerned  in  puer- 
peral infection  has  confirmed  the  old  observation  of  clinicians  as  to 
the  relationship  between  this  disease  and  e^sipelas.  It  should  not 
be  believed,  however,  that  a  puerperal  woman  suffering  from  erysi 
elas  is  condemned  to  develop  septicemia.  The  results  obtained  by  us 
are  of  a  nature  to  render  the  diagnosis  far  less  pessimistic.2  Nineteen 
patients  affected  with  erysipelas  were  confined  in  our  wards  without 
the  occurrence  of  any  symptoms  of  importance.  The  prognosis  is 
not  any  worse  when  erysipelas  supervenes  after  confinement.  ^  e 
received  nine  women  under  these  conditions:  all  recovered  readily. 

There  is  also  a  category  in  which  puerperal  infection  appears  spon- 
taneously. Although  the  number  of  such  cases  is  decreasing  with 
the  advance  of  asepsis,  the  possibility  of  autogenic  infection  may  be 
admitted.  The  microbes  develop  owing  to  a  profoundly  weakened 
condition  of  the  organism,  and  infection  is  then  prepared  by  digestive 

1  Petruschky.  Untersuchuiigen  liber  Infektiou  mit  pyogenen  Kokken.  Z<?itschr.  fur 
Hygiene,  1894. 

2  Roger.     iitude  elinique  de  l'erysipele.     Rev.  de  nied.,  1S96,  p.  236. 


262  INFECTIOUS  DISEASES. 

disturbances,  putrid  fermentations  in  the  intestine,  or  some  intercur- 
rent affection,  as  well  as  by  the  retention  of  placental  remains.  The 
last-named  incidenl  is  of  frequent  occurrence,  and  gives  rise  to  putre- 
factions under  the  influence  of  saprophytes ;  the  products  thus  orig- 
inated favor  infection  considerably. 

We  will  not  dwell  at  length  upon  the  causes  of  surgical  infection. 
In  some  cases  the  wound  is  contaminated  with  germs,  and  general 
infection  follows  at  once.  In  other  instances  a  local  lesion  is  first 
produced,  which  subsequently  gives  rise  to  general  infection.  Lastly, 
infection  may  result  from  traumatism  unattended  by  any 
wound.  Facts  of  the  last  category  are  exceptional.  Wagner  has 
reported  a  remarkable  example :  it  was  a  case  of  pyemia  consecutive 
to  a  fall  upon  the  hip.  When,  however,  bacteremia  is  consecutive 
to  a  wound,  it  is  not  at  all  necessary  for  the  latter  to  be  a  large  one ; 
serious  phenomena  have  been  seen  to  follow  slight  traumatism. 
Landois  cites  a  case  of  pyemia  following  a  leech  bite.  It  must  be 
acknowledged,  however,  that  infection  is  favored  by  all  causes  that 
produce  severe  attrition  in  soft  tissues.  Disinfection  of  such  wounds 
is  difficult,  and  microbes  find  in  contused  and  altered  parts  conditions 
favorable  to  their  development.  Finally,  with  regard  to  surgical  as 
well  as  puerperal  infections,  the  dominant  etiological  factor  resides 
in  the  transportation  of  germs  by  the  hands  of  the  operator  or  by 
poorly  sterilized  instruments. 

The  last  group,  which  also  belongs  in  the  domain  of  surgery  and 
medicine,  comprises  those  cases  in  which  bacteremia  is  consecutive 
to  an  old  lesion,  for  instance,  suppurating  wounds  or  deep-seated 
lesions  which  scarcely  admit  of  disinfection.  It  has  already  been 
stated  in  connection  with  the  process  of  suppurations  that,  in  order 
to  explain  generalization,  it  is  necessary  to  assume  a  previous  modi- 
fication of  the  organism,  probably  through  the  agency  of  microbic 
products  originating  in  the  primary  focus. 

If  we  now  pass  to  medical  affections,  we  likewise  see  that  there  is 
no  constant  relation  between  the  gravity  of  the  primary  lesion  and 
its  tendency  to  generalization.  Cutaneous  suppurations,  notably 
those  of  smallpox,  alterations  of  the  tonsils,  intestinal  ulcerations, 
lesions  of  the  liver,  urinary  passages,  and  lungs,  are  the  most  frequent 
causes  of  infection. 

Lastly,  there  remains  the  group  of  cryptogenetic  septicemias  in 
which  general  infection  seems  to  occur  spontaneously.  This  group 
may  be  divided  into  two  secondary  groups.    The  initial  lesion  some- 


SEPTICEMIAS  AND  PTEMIA8.  268 

times  remains  unnoticed,  no1  having  revealed  il  elf  during  life  by 
any  appreciable  symptom;  it  existed,  neverthele  ,  and  wa  found 
at  the  necropsy.  Ii  may  be  a  visceral  uppuration,  an  intestinal 
ulceration,  an  old  locus  within  omi  gland,  etc.  There  are,  bow 
oilier  instances  in  which  the  mosl  searching  post-mortem  examina- 
tion reveals  no  previous  lesion  infection  bas  been  effected  in  the 
absence  of  any  starting  point,  [ncertainca  i  il  development  may 
be  accounted  for  bya  previous  state  of  general  debility.  It  is  highly 
probable  thai  penetration  of  microbes  into  the  system  occur-  con- 
stantly, but  they  do  mischief  only  when,  as  a  resull  of  exhaustion 
from  overwork,  or  cold,  or  some  other  cause,  the  organism  i-  unable 
to  destroy  the  germs.  Ii  is  to  be  acknowledged,  however,  thai  there 
are  cases  of  infection  which  defy  all  explanation  no  cause  can  be 
found  to  account  for  their  development. 

Infection  may  evolve  as  a  septicemia  without  any  localization. 
The  disease  is  characterized  by  intense  initial  chills,  continued 
fever,  and  a  grave  general  state.  The  prognosis,  however,  is  often 
less  serious  than  in  cases  of  surgical  or  puerperal  septicemia. 

From  the  beginning  or  at  a  later  period  septicemia  may  become 
localized  in  a  viscus.  At  times  localization  is  not  clear,  and  must  be 
carefully  looked  for,  or  it  may  seem  to  be  of  little  importance,  as  is 
the  case  when  it  is  expressed  by  an  attack  of  albuminuria  or  the 
development  of  an  erythema.  In  other  instances  visceral  localiza- 
tion is  the  striking  feature,  while  the  septicemic  phenomena  tend  to 
amelioration.  In  such  cases  septicemia  represents  a  period  of  tran- 
sition leading  to  infectious  localization,  which  then  constitutes  the 
disease  and  develops  on  its  own  account.  It  is  not  rare  to  meet  with 
records  of  such  instances  in  which  general  infection  is  scarcely  referred 
to,  although  it  has  been  the  cause  of  the  localization  which  selects 
the  heart,  vessels,  lungs,  or  the  liver,  and  may  result  in  ulcerative 
endocarditis,  arteritis,  phlebitis,  bronchopneumonia,  acute  nephritis, 
or  diffuse  hepatitis. 

These  various  localizations  are  simply  of  an  inflammatory  nature: 
in  other  cases,  however,  they  may  be  expressed  by  suppurative 
lesions ;  septicemia  then  terminates  in  pyemia.  It  is  certainly  difficult 
to  say  why  a  septicemic  pathogenic  agent  may  sometimes  give  rise 
to  suppuration.  Some  authors  assume  that  the  purulent  function 
already  denotes  a  certain  degree  of  reaction  on  the  part  of  the  system, 
and  that  it  may  be  accounted  for  by  a  moderate  virulence  of  the 
infectious  agent.     This  same  explanation  has  received  a  more  scien- 


264  IXFECTIOUS  DISEASES. 

title  formula.  According  to  Sittmann,  septicemia  is  of  a  toxico- 
infectious  nature:  it  occurs  when  bacteria  find  in  the  organism  con- 
ditions favorable  for  the  production  of  poisons;  in  the  contrary  case 
the  bacteria  are  in  part  destroyed,  and  the  proteins  of  their  cadavers 
excite  the  formation  of  pus. 

The  articular  localizations  of  pj^emia  had  long  been  confounded 
with  articular  rheumatism  when  Lasegue  and  Quinquaud  individ- 
ualized them.  The  latter  author  has  described  them  under  the  name 
arthrito-suppurative  disease.  The  works  of  Prof.  Bouchard  and 
Bourcy  have  conclusively  established  the  nature  of  these  infectious 
pseudorheumatisms  which  sometimes  occur  in  a  primary  manner  and 
sometimes  appear  in  the  course  of  or  subsequently  to  the  most  varied 
infections.  What  essentially  characterizes  this  clinical  type  is  that 
the  process  involves  only  a  small  number  of  joints;  the  lesions  mani- 
fest a  great  tendency  to  become  localized  by  preference  in  the  knee- 
joint,  to  undergo  purulent  transformation,  or  terminate  in  ankylosis. 
This  limitation  of  the  process  to  a  joint  contrasts  with  the  tendency 
of  polyarticular  rheumatism  to  affect  successively  various  joints. 
Moreover,  sweating  and  polyuria  are  absent  in  the  former  instance 
and,  finally,  salicylate  of  soda  is  useless  in  such  cases. 

Pyemia  with  cutaneous  or  subcutaneous  determinations  is  less 
common.  In  the  former  case  infectious  erythemas  and  purpura 
develop,  with  formation  of  pustulse  and  bullae  filled  wdth  pus.  There 
is  a  clinical  type  in  which  the  eruption  of  pustules,  the  so-called 
pustules  of  Colles,  are  produced  after  an  abrupt  invasion  character- 
ized by  chills,  fever,  and  rachialgia.  These  manifestations  subside 
when  the  eruption  appears.  The  latter  consists  of  small  pustules 
surrounded  by  a  red,  inflammatory  zone.  At  first  sight  variola  may 
be  suspected,  but  a  more  attentive  examination  will  enable  one  to 
differentiate  this  subepidermic  eruption  from  the  eruption  of  small- 
pox. 

As  an  illustration  of  pyemias  with  subcutaneous  determinations 
we  may  cite  an  observation  of  Broca :  A  woman,  aged  twenty-nine 
years,  while  nursing  a  patient  with  erysipelas,  complained  of  malaise  ; 
ten  days  later  she  had  chills  and  then  developed  multiple  phlegmons. 
Death  occurred  on  the  sixteenth  day,  and  the  necropsy  demonstrated 
the  absence  of  any  purulent  focus  in  the  viscera. 

Attenuated  Forms  of  Septicemias  and  Pyemias.  The  expressions 
septicemia  and  pyemia  suggest  the  idea  of  a  serious,  commonly  fatal 
process.     Along  with  the  acute  forms,  however,  should  be  classed  a 


SEPTICEMIAS  AND  PYEMIA8. 

certain  number  of  cases  in  which  the  procei    become    localized  and 
lends  bo  resolution.    The  manifestations  may  even  be  of  an  ephem- 
eral character.    Traumatic  fever  and  milk  fever  are  nothing  bul 
septicemic  fevers  so  benign  as  to  subside  in  fcwenty-four  or  f< 
eight  hours.    The  same  is  true  as  regards  certain  urinary  fev<  i 
very  short  duration. 

These  remarks  are  also  applicable  to  pyemias.  Although  the  forms 
in  which  numerous  visceral  foci  exisl  are  necessarily  fatal,  there  are 
also  benign  forms  in  which  localization  takes  place  in  some  tissue, 
for  instance,  in  a  joint,  and  in  which  cure  is  effected  by  a  surgical 
operation.  Kven  in  grave  eases  of  generalized  i nice i  ions  recovery  has 
sometimes  been  obtained.  If  is  mostly  in  septicemia  without  pro- 
found cellular  lesions  that  this  happy  result  can  be  seen.  In  C 
of  generalized  visceral  pyemia  attenuation  or  even  destruction  of  the 
agent  avails  nothing;  the  patient  succumbs,  not  to  the  infection,  bu1 
to  the  visceral  lesions  resulting  therefrom. 

Variola,  Pyemia  and  Septicemia. 

The  relations  existing  between  septicemias  and  pyemias  are  clearly 
evidenced  by  the  study  of  a  specific  infection,  variola, 

The  virus  penetrates  into  the  organism,  probably  through  the 
respiratory  passages  and  invades  the  blood.  Then  reactionary  mani- 
festations of  extreme  violence  appear.  If  the  virus  is  very  energetic 
it  produces  profound  cellular  lesions  and  marked  alterations  in  the 
blood.  Erythemata,  purpura,  hemorrhages  in  the  skin,  mucous 
membranes,  and  principal  organs  are  among  the  frequent  events. 
The  individual  succumbs  in  the  absence  of  any  tendency  to  suppu- 
ration.    It  is  a  case  of  genuine  hemorrhagic  septicemia. 

If  the  virus  is  less  powerful,  the  expulsion  of  the  parasite  may  be 
effected.  The  organism  eliminates  it  through  the  mucous  mem- 
branes and  the  skin,  and  papules  appear  at  the  various  points  by 
which  the  microbes  are  rejected.  A  struggle  is  begun  against  the 
pathogenic  agent  which  results  in  the  formation  of  pustules.  There 
is  no  intervention  on  the  part  of  pyogenic  cocci  ever  present  in  the 
mucous  membranes  and  integuments:  suppuration  is  due  to  the 
specific  agent  which  thus  gives  rise  to  a  pyemia  with  cutaneous 
determination. 

Between  the  two  extreme  types  there  are  numerous  transitions. 
In  certain  cases,  in  the  course  of  variolar  septicemia,  the  organism 
makes  a  last  effort  which  is  expressed  by  the  development  of  a  few 


266  IXFECTIO  US  DISEASES. 

irregularly  distributed  pustules.  On  the  other  hand,  a  suppurating 
variola  may  become  modified  in  its  progress  by  the  occurrence  of 
secondary  hemorrhages.  Lastly,  there  exist  some  mixed  cases  of 
infection  in  which  pustules  and  hemorrhages  make  their  appearance 
synchronously. 

These  facts  lead  us  to  the  conclusion  that  the  pustules  are  the 
result  of  the  struggle  against  the  parasite.  When  the  virus  is  very 
active  the  eruption  is  not  produced;  the  patient  succumbs  to  hemor- 
rhagic septicemia.  In  fact,  out  of  forty  patients  with  primary 
hemorrhagic  variola  admitted  into  our  wards,  none  recovered. 

In  cases  of  pustular  variola,  the  eruption  is  intense  in  proportion 
to  the  abundance  of  the  virus.  From  cases  with  confluent  pustules 
down  to  those  in  which  the  pustules  are  extremely  rare  or  altogether 
absent,  there  are  numerous  intermediate  degrees.  The  cases  with 
no  eruption  are  recognized  only  at  the  time  of  an  epidemic.  An 
individual  who  has  been  exposed  to  contagion  suffers,  fifteen  days 
later,  from  chills,  fever,  and  rachialgia.  Four  days  later  the  symp- 
toms tend  to  disappear  without  the  appearance  of  eruption.  Were 
it  not  for  the  etiological  data  derived  from  the  circumstances,  a 
diagnosis  would  be  impossible.  These  facts  were  known  to  ancient 
clinicians.  Modern  hematological  researches  have  demonstrated 
their  reality  beyond  all  doubt  by  showing  in  the  blood  the  presence  of 
the  special  mononucleosis  which  is  characteristic  of  variolar  infection. 

The  ideas  above  expressed  do  not  agree  with  the  opinions  of  certain 
authors  who  attribute  to  secondary  infections  a  primordial  role  in 
the  evolution  of  variola.  Some  explain  in  this  manner  the  purulent 
transformation ;  others  admit,  with  Hlava,  that  hemorrhagic  variola 
is  due  to  microbic  association;  superadded  bacteria  are  supposed  to 
modify  the  course  and  aspect  of  the  disease.  It  is  true  that  pyogenic 
bacteria  are  always  found  in  the  pustules,  at  least  at  an  advanced 
stage  of  their  evolution,  and  that  the  streptococcus  is  constantly 
detected  in  the  blood  and  organs  at  the  necropsy.  In  cases  of 
hemorrhagic  variola  this  microbe  is  at  times  detected  in  the  blood 
during  life.  Hence,  some  bacteriologists  considered  the  strepto- 
coccus as  the  specific  agent  of  the  disease  and  designated  it  the 
mriolococcus.  The  author  believes  too  much  importance  is  ac- 
corded to  this  microbe,  which  must  be  looked  upon  simply  as  a 
superadded  agent  aggravating  the  prognosis.  He  does  not  regard 
it  as  the  cause  of  the  suppuration,  since  pustules  may  contain  no 
streptococci.    He  has  often  examined  or  sown  the  pus  without  being 


SEPTICEMIAS  AND  PYEMIA8.  267 

able  to  detect  any  bacteria  which  could  I"-    tained  or  cultivated  by 
our  present  methods.    In  one  case  blood  was  drawn  one  hour  before 
death  from  the  vein  of  the  elbow  of  a  patienl  suffering  from  prin 
hemorrhagic  variola,  and   neither  the  streptococcus  nor  any  other 
bacterium  was  found.     Pyogenic  bacteria  may  likewise  be  ab 
from  even  suppurative  visceral  lesion 

On  the  other  hand,  experimentation  demonstrate  thai  the  pus 
and  at  times  the  blood  are  virulent.  Their  inoculation  into  the 
rabbit  is  followed  by  the  development  of  a  fatal  disease  which, 
under  certain  conditions,  may  be  transmitted  in  series.  The  blood 
of  the  inoculated  animals,  taken  during  life,  proves  virulent, 
although  it  is  also  devoid  of  bacteria. 

Rejecting  the  bacterial  origin  of  variola,  we  are  led  to  the  question 
whether  this  disease  is  nol  due  to  special  parasites,  and  notably  to 
the  protozoa  that  have  been  described  by  a  few  authors. 

Microbiology  of  Variola.  Dr.  Renaul  was  the  firsl  to  point  out, 
in  1881,  special  corpuscles  in  the  pustules  which  he  held  to  be  para- 
sites and  to  which  he  attributed  a  mechanical  action  in  the  formation 
of  the  cutaneous  cavity.  Van  der  Loeff  gave  a  fairly  exacl  descrip- 
tion of  these  elements  and,  about  the  same  time,  L.  Pfeiffer,  widening 
the  range  of  the  debate,  published  a  series  of  highly  interesting 
researches  upon  the  role  of  protozoa  in  the  development  of  infections 
and  notably  in  vaccinia  and  smallpox.  Guarnieri  inoculated  the  pus 
of  variola  or  the  fluid  of  vaccinia  into  the  cornea  of  the  rabbit:  a 
pustule  developed,  the  stud)-  of  which  showed  strange  figures  inter- 
preted by  the  author  as  the  various  phases  of  the  evolution  of  the 
parasite.  From  that  time  onward  various  contributions  appeared, 
and  now  there  is  general  agreement  as  to  the  presence  of  small 
special  elements  in  the  fluids  of  variola  or  vaccinia.  It  was  rela- 
tively easy  to  see  these  corpuscles,  but  difficult  to  determine  their 
nature  and  significance.  "While  the  above-mentioned  authorities 
considered  them  as  parasites,  others  could  not  see  in  them  anything 
but  simple  nuclear  detritus.  Such  was  the  opinion  of  Salmon.1  to 
whom  we  owe  a  remarkable  work  of  experimental  criticism  on  this 
subject. 

From  the  very  beginning  of  our  researches  on  variola2  we  have 

1  Salmon.  Recherches  sur  1 'infect ion  dan*  La  vaccine  et  la  variole.  Annates  de 
l'Institut  Pasteur,  April.  1897. 

2  Roger  and  Weil.  Inoculabilite  de  la  variole  humaine  an  lapin.  Soc.  de  biologie, 
November  10,  1900.  Recherches  microbiologiques  sur  la  variole.  Ibid..  November 
17,  1900.      Recherches  sur  le  parasite  de  la  variole.  Presse  med..  November  2$.  1900. 


268  ISFECTIO  US  DISEASES. 

noticed  these  special  elements,  and  we  have  constantly  observed 
them  in  both  man  and  inoculated  animals. 

It  is  not  easy,  however,  to  recognize  these  special  elements.  Some 
of  them  are  very  small  and  do  not  measure  more  than  1/t;  they  may 
then  be  confounded  with  micrococci.  The  largest  elements  attain  a 
length  of  3«  and  simulate  leucocytes.  They  are  likewise  found  in 
the  blood,  even  in  cases  of  varioloid.  They  are,  however,  more 
numerous  in  grave  cases  and  particularly  abundant  in  hemorrhagic 
forms.  And  j^et,  even  in  the  latter  case,  it  is  often  necessary  to 
examine  the  preparation  for  a  long  time  and  search  several  fields  of 
the  microscope  in  order  to  detect  a  single  element.  In  the  hemor- 
rhagic forms  the  corpuscles  are  present  in  all  extravasations  of 
blood,  in  hematoma,  and  in  the  urine  in  the  case  of  hematuria;  the 
necropsy  reveals  their  presence  in  the  various  organs,  especially  in 
the  spleen  and  bone-marrow. 

Without  dwelling  upon  all  the  arguments  which  tend  to  demon- 
strate that  these  corpuscles  are  not  cellular  detritus,  we  shall  mention 
two  necropsies  which  we  had  the  opportunity  of  making  at  the  begin- 
ning of  our  researches.  Two  pregnant  women,  one  of  five  and  the 
other  of  six  months,  having  died  from  confluent  variola,  we  took  the 
amniotic  fluid  which,  in  both  instances,  was  clear  and  transparent. 
Microscopic  examination  showed  no  leucocytes,  but  only  desqua- 
mated epidermic  cells  originating  from  the  fetus  and  a  considerable 
number  of  corpuscles;  we  had  never  seen  such  a  great  number  of 
them.  As  the  possibility  of  leucocytic  detritus  was  precluded,  it 
seemed  to  us  rational  to  admit  that  we  were  in  the  presence  of  para- 
sites that  had  invaded  the  fetuses,  in  whose  bodies  a  great  quantity 
of  them  was  found,  and  had  contaminated  the  amniotic  fluid.  The 
motility  of  these  elements  in  the  amniotic  fluid  further  confirmed  our 
view.  They  moved  here  with  sufficient  rapidity,  while  their  move- 
ment was  not  clear  enough  in  the  pus. 

In  order  to  be  able  to  conclusively  determine  the  nature  and  role 
of  the  corpuscles,  it  was  necessary  to  resort  to  experimentation. 

Experimental  Variola  of  the  Rabbit.  We  looked  for  an  animal 
sensitive  to  the  variolar  virus,  and  we  found  the  rabbit  to  be  such. 

If  variolar  pus  free  from  bacteria  and  containing  corpuscles  only 
is  inoculated  into  a  rabbit,  the  result  is  usually  a  fatal  disease.  If 
the  inoculation  is  made  into  the  anterior  chamber  of  the  eye,  a  thick 
exudate  generally  occurs  at  the  end  of  twenty-four  or  forty-eight 
hours,  and  heals  up  in  five  or  six  days.    In  spite  of  the  disappearance 


SEPTICEMIAS  AND  PYEMIAS.  269 

of  the  local  lesion  the  animal  continues  to  emaciate  and  dies  on  the 
tenth  to  the  twentieth  day  after  inoculation,  [f  the  pus  La  introduced 
beneath  the  skin  or  injected  into  the  veins,  death  supervenes,  as  in 
the  previous  instance,  at  the  end  of  two  or  three  weeks. 

The  disease  thus  produced  differs  from  human  variola.  The  ele- 
ment which  seems  to  !"■  characteristic  i.  e.,  the  pustule  and  which 
only  exceptionally  is  absent  in  man  i-  3eldom  observed  in  rabbits. 
In  three  instances  we  saw  a  few  papules  develop  on  the  fourth  day 
in  the  region  corresponding  to  the  subcutaneous  inoculation,  and 
then  resolve  in  forty-eighl  hours.  In  one  instance  the  eruptions  were 
more  profuse,  aboul  twenty  in  number. 

It  is  not  without  interest  to  note  that,  although  the  variola  of  the 
rabbil  differs  from  thai  of  the  human  adult,  it  resembles  the  variola 
of  the  newborn.  Children  born  of  contaminated  mothers  succumb 
to  a  slow  septicemia.  At  times  the  eruplion  is  altogether  absent; 
in  other  cases  there  are  but  a  few  disseminated  papules  which,  like 
those  of  the  rabbit,  become  covered  with  a  crust  and  desiccate  with- 
out suppurating. 

Bacteriological  examination  frequently  reveals  in  man,  as  a  super- 
added bacterium,  the  streptococcus,  more  rarely  the  pneumococcal 
while  in  animals  a  large  bacillus  is  generally  found.  It  is  important 
to  remark,  however,  that  in  two  out  of  every  three  cases,  no  microbe 
whatever  can  be  detected  in  the  inoculated  animals,  while  the  cor- 
puscles are  constantly  found.  These  possess  the  same  appearance 
and  characters  as  in  man. 

The  presence  of  these  peculiar  elements  establishes  a  new  analogy 
between  human  and  animal  variola.  This  is  not,  however.  abso- 
lutely demonstrative  of  the  parasitic  nature  of  the  corpuscles,  since 
it  may  be  argued  that  the  phenomenon  is  one  of  special  alteration 
produced  in  the  cells  of  the  organism  by  the  variolar  virus.  It  was. 
therefore,  necessary  to  follow  the  development  of  these  corpuscles 
outside  the  animal  system. 

Cultivation  of  the  Microbe  of  Variola.  We  first  studied  what 
occurs  when  the  blood  of  the  infected  animal  is  placed  in  the  incu- 
bator at  a  temperature  of  100.4°  F.  (38°  C.)  for  twenty-four  hours. 
At  the  end  of  this  period,  microscopic  examination  showed  that  the 
number  of  the  corpuscles  was  considerably  increased.  Still  the 
increase  was  restricted  and  could  not  be  compared  with  the  rapid 
multiplication  of  bacteria. 

The  next  point  requiring  investigation  was  whether  the  corpuscles 


270  IXFECTIO  US  DISEASES. 

which  multiplied  in  the  blood  taken  from  the  infected  animal  could 
equally  develop  in  the  blood  of  normal  animals.  Starting  with  the 
blood  of  an  infected  rabbit  that  had  been  kept  in  the  incubator  for 
forty-eight  hours,  we  once  obtained  eighteen  successive  cultures. 
The  corpuscles  readily  developed  in  them,  retaining  their  primary 
characters,  except  that  they  were  somewhat  larger  in  size,  2.5//  and 
at  times  3,«. 

It  seems,  therefore,  reasonable  to  conclude  that  these  elements  are 
true  parasites.  It  is  hardly  necessary  to  add  that  we  have  often 
assured  ourselves  that  the  blood  of  normal  rabbits  submitted  to  the 
same  process  never  presents  such  corpuscles. 

A  last  point  to  be  settled  by  experimentation  still  remained,  viz., 
the  effects  produced  in  rabbits  by  the  inoculation  of  our  cultures. 

We  made  the  same  experiments  as  with  the  pus  of  variola,  to  wit, 
we  inoculated  into  the  anterior  chamber  of  the  eye,  beneath  the  skin 
and  into  the  veins,  with  substantially  the  same  local  and  general 
results,  including,  in  some  cases,  the  production  of  a  small  number 
of  papules,  and  terminating  in  death  within  a  period  of  fifteen  to 
thirty  clays. 

Conclusions.  Such  are  the  results  obtained  bjr  the  experimental 
study  of  variola.  Although  numerous,  our  observations  and  re- 
searches are  insufficient  and  incomplete.  We  may,  nevertheless, 
draw  some  conclusions  from  the  accumulated  facts. 

As  the  corpuscles  multiply  outside  the  organism,  in  the  blood  of 
infected  animals,  and  even  in  defibrinated  normal  or  incoagulable 
blood,  there  is  no  logical  escape  from  the  conclusion  that  we  have 
to  deal  not  with  altered  cells,  but  a  parasite,  probably  a  sporozoon, 
especially  when  we  remember  the  fact  that  these  corpuscles  are  also 
found  in  the  amniotic  fluid. 

Although  as  yet  incomplete,  our  experiments  have  some  practical 
bearings.  The  parasites  which  we  studied  being  invariably  present 
in  variola  patients,  we  have  been  able,  according  as  they  were  present 
or  absent  in  cases  of  doubtful  diagnosis,  to  admit  or  reject  the  variolar 
nature  of  the  disease,  and  our  conclusions  were  confirmed  by  the 
ulterior  evolution  of  the  cases.  We  must  remark  that  variola  is  not 
the  only  infection  in  which  these  elements  are  encountered;  similar 
agents  are  also  found  in  cases  of  vaccinia  and  varicella.  This  does 
not  necessarily  mean  that  these  infections  are  all  due  to  a  unique 
agent,  or  that  they  are  to  be  considered  as  various  forms  of  the  same 
disease.     These  results  merely  indicate  the  relationship  of  the  patho- 


SEPTICEMIAS  AND  PYEMIAS.  271 

genie  agents.  Clinical  observers  have  long  been  abb  bo  compare 
certain  eruptive  fevers  to  variola.  As  is  generally  the  case  in  Buch 
matters,  the  analogies  were  first  seen.  Variola  and  varicella  have 
for  a  long  time  been  identified.  The  identity  of  variola  with 
vaccinia  has  long  been  and  is  still  ;i  subjeel  of  controversy.  The 
microbiological  study,  in  its  presenl  stage  of  development,  shows 
rather  reseinhl.'iiices;  l:iier  on  \i  will  reveal  differential  characters. 


CHAPTER   X. 

NODULAR  INFECTIONS. 

Mode  of  Development  and  Signification  of  Infectious  Granulations.  Infectious  Nodules. 
Microscopic  and  Macroscopic  Nodules.  Glanders.  Characters  of  the  Granula- 
tions of  Glanders;  Their  Analogy  to  Suppurative  Lesions  and  to  Tubercles. 
General  Considerations  on  the  Bacteriology,  Etiology,  and  Nosolog3r  of  Glanders. 
Tuberculosis.  Characters  of  the  Tubercle  Bacillus.  Mode  of  Propagation  of 
Tuberculosis.  Pathological  Anatomy  of  Tubercle.  Histogenesis.  Tubercular 
Toxins.  Sensitive  and  Refractory  Animals  with  Regard  to  Tuberculosis.  Tuber- 
culosis of  Various  Mammalia.  Avian  Tuberculosis.  Tuberculosis  of  the  Gallinaj; 
its  Relation  to  Human  Tuberculosis.  Tuberculosis  of  the  Psittaci.  Unity  of 
Tuberculosis.  Pseudotuberculosis.  Study  of  Bacillary  Pseudotuberculosis. 
Oidiomycosis  or  Endomycosis.  Biology  of  the  Oidium  Albicans;  its  Action  on 
Man  and  Animals.  Oidian  Granulations.  Oidian  Toxins.  Vaccination  and 
Modification  of  the  Serum  in  Animals  Vaccinated  against  the  Oidium  Albicans. 
Infections  Produced  by  Yeasts.  Actinomycosis.  Characters  of  the  Parasite. 
Etiology  of  Actinomycosis;  its  Characters  in  Animals  and  in  Man.  The  Various 
Pathogenic  Streptothrixae.  Infections  Due  to  Mucedinse  and  Aspergillus.  Rela- 
tion between  Tumors  and  Infections.  Inflammatory  Tumors.  Experimental 
Tumors. 

The  development  of  microbic  colonies  often  becomes  a  point  of 
attraction  for  wandering  cells  which  accumulate  in  the  form  of 
microscopic  nodules.  These  are  the  infectious  nodules,  for  the  knowl- 
edge of  which  we  are  indebted  to  Friedrich  and  E.  Wagner.  They 
are  considered  by  many  authorities  to  be  accumulations  of  cells 
surrounding  and  circumscribing  a  microbic  focus.  This  conception 
is  inexact,  since  such  formations  may,  experimentally,  be  obtained, 
especially  in  the  liver,  by  injection  of  toxins.  I  have  noted,  for 
instance,  that  the  soluble  products  of  the  B.  septicus  putidus  give 
rise  to  the  development  of  nodules;  the  only  difference  lies  in  the 
fact  that  the  nodules  then  appear  more  rapidly  than  in  animals 
infected  by  living  cultures. 

These  nodules  are  held  to  be  formed  by  round,  indifferent  cells, 
at  times  designated  under  the  improper  name  of  embryonal  cells, 
which  are  sometimes  supposed  to  have  originated  on  the  spot, 
sometimes  to  have  migrated  from  the  vessels.  Investigations  have 
convinced  me,  however,  that  the  constitution  of  these  nodules  is 
far  more  complex  and  varies  according  to  the  disease  considered. 
These  productions  may  be  expressed  in  cytological  formulae  exactly 


NODULAR  INFECTIONS.  -rr.\ 

corresponding  to  those  of  the  blood.  Thui  in  variola1  the  nodulec 
of  the  liver  are  constituted  by  more  voluminou  mononuclears. 
Some  have  a  clear  nucleus  surrounded  by  8  protoplasm  which  can 
be  deeply  stained;  others  contain  a  dark  nucleus  and  a  variable 
amount  of  indifferent  protoplasm.  These  cells  are  mingled  with 
connective  (issue  cells.  The  granular,  inconstanl  cell  are,  in  some 
instances,  quite  numerous:  these  are  eosinophilic  polynucl 
neutrophilic  mononuclears,  and  a  few  neutrophilic  polynucl 
Thus  the  same  elements  are  found  in  the  variolar  nodulec  as  in  the 
hematopoietic  organs,  a  fad  which  leads  to  the  question  whether 
these  nodules  express  a  defensive  reaction  capable  of  arousing  a 
cytopoictic  function  which  seemed  In  he  extinct. 

The  diseases  characterized  by  granulations  establish  a  transition 
between  pyogenic  infections  and  neoplasms.  Certain  pseudo- 
tuberculoses resemble  genuine  tuberculosis  in  their  macroscopic 
characters;  histological  examination  shows,  however,  that,  in  the 
former  case,  the  granulation  is  simply  made  up  of  a  mass  of  unaltered 
round  cells. 

The  histoiy  of  tuberculosis  furnishes  a  remarkable  illustration  of 
the  relations  existing  between  suppurations,  granulations,  and  neo- 
plasms. In  a  certain  number  of  cases  Koch's  bacillus  gives  rise  to 
cold  suppurations ;  it  acts  like  a  simple  pyogenic  agent.  By  a  more 
energetic  action,  it  causes  the  formation  of  tubercles,  the  structure 
of  which  is  far  more  complex  and  characterized  by  the  development 
of  epithelioid  and  giant  cells.  It  is  almost  a  tumor.  In  certain 
animals  the  neoplastic  evolution  is  complete;  in  the  dog.  tuberculosis 
is  expressed  by  productions  presenting  the  appearance  of  sarcoma 
and  lymphadenoma.  Microscopic  examination  alone  is  not  suf- 
ficient to  reveal  the  nature  of  these  tumors ;  in  order  to  demonstrate 
their  tubercular  origin  it  is  necessarj^  to  resort  to  inoculation. 

In  the  same  order  of  ideas  we  may  cite  actinomyces  which  some- 
times produces  suppurating  foci,  and  sometimes  lesions  that  have 
long  been  confounded  with  sarcoma. 

In  fact,  it  is  well  known  that  the  most  commonplace  inflammatory 
lesions  may  be  followed  by  the  development  of  a  cancer.  It  is 
hardly  necessary  to  refer  to  the  transitions  which  relate  simple 
gastritis  to  polyadenomata  and  epitheliomata  of  the  stomach.  The 
line  of  relationship  may  thus  be  followed  through  these  various 

1  Roger  and  'Weil.  Note  sur  les  nodules  infectieux  du  foie  d:\ns  la  variole.  Soc.  de 
biologie,  November  3,  1900. 

IS 


274  INFECTIOUS  DISEASES. 

morbid  processes.  I  had  the  opportunity  to  observe  an  experi- 
mental fact  comparable  thereto.  The  inoculation  of  the  staphylo- 
coccus aureus  Into  the  thyroid  artery  gave  rise  to  the  development 
of  a  true  tumor.  I  by  no  means  wish  to  affirm  the  infectious  origin 
of  cancer.  I  believe,  nevertheless,  that  these  few  examples  suffice 
to  show  the  reason  why  I  place  nodular  diseases  in  a  separate  class 
forming  a  transition  between  purulent  infections  and  tumors. 

Now,  if  we  consider  the  entire  group  of  diseases  characterized  by 
granulations  or  nodules,  we  find  the  following  in  their  order  of  in- 
creasing complexity: 

Glanders,  which  is  rather  akin  to  purulent  infections; 

Bacterial  pseudotuberculosis ; 

K 1  ycotic  pseudotuberculoses ; 

True  tuberculosis,  and 

Actinomycosis. 

Glanders. 

Glanders  is  a  virulent,  contagious,  and  inoculable  disease,  occurring 
particularly  in  the  horse,  the  ass,  and  the  mule,  and  may  accidentally 
be  transmitted  to  various  other  animal  species  as  well  as  to  man. 

Although  one  disease  by  nature,  glanders  may  appear  under 
various  clinical  aspects. 

Biology  of  the  Bacillus.  The  bacillus  of  glanders  appears  in  the 
form  of  small,  straight,  or  slightly  curved  rods,  with  rounded  ends. 
It  is  non-motile  or  endowed  with  simple  molecular  movements..  It 
is  very  much  like  the  bacillus  of  tuberculosis,  but  is  a  little  thicker, 
measuring  from  2;i  to  5//  in  length  and  0.2/^  to  0.5//  in  breadth.  It 
is  readily  stained  by  various  aniline  dyes,  particularly  by  alkaline 
solutions,  but  is  decolorized  by  Gram's  as  well  as  by  Weigert's 
method. 

Being  a  facultative  anaerobic,  the  bacillus  of  glanders  readily 
develops  in  the  various  media  employed  in  bacteriology,  provided, 
however,  it  is  placed  at  a  sufficiently  high  temperature — i.  e.,  at 
98.6°  or  100.4°  F.  (37°  or  38°  C.).  A  temperature  of  131°  F.  (55°  C.) 
destroys  the  culture.  According  to  Babes,  the  bacillus  taken  from 
man  or  the  horse  does  not  develop  except  upon  potatoes  or  in 
bouillon;  it  can  grow  in  agar-agar  only  after  it  becomes  habituated 
to  these  media, 

The  bacillus  of  glanders  can  hardly  resist  the  causes  of  destruction 
—exposure  to  air,  sunlight,  and  heat,  putrefaction,  etc.     The  secre- 


NODULAR  INFECTIONS.  275 

tions  of  glandered  animals  rapidly  lose  their  virulence;  the  pus 
thinly  spread  and  placed  in  a  confined  enclo  lire  become    Inj 
;ii  the  end  of  two  days,  while  in  the  central  parte  of  an  organ  the 
virulence  may  persisl  for  twentj  six  day   (Cadeucand  Mallet).    The 
cultures  resisl  longer,  for  a  period  of  three  or  four  month     Loeffler). 

Animals  Sensitive  or  Refractory  to  Glanders.  The  animate  mosl 
liable  to  contracl  glanders  are  the  horse,  the  ass,  the  mule.  Sheep 
and  goats  also  contracl  ii  easily,  even  spontaneously.  The  bovidas 
are  completely  immune. 

An  ulcer  which  extends  a  little  and  then  cicatrizes  and  heals  i- 
observed  at  the  point  of  inoculation  in  the  dog.  The  ca1  is  highly 
sensitive  to  glanders;  ;it  the  end  of  eigjbl  days  its  articulations 
are  invaded,  and  it  often  succumbs  within  two  weeks  (Lisitcyn  . 
The  disease1  has  also  been  observed  in  wild  animals  Qourished  in 
menageries  with  contaminated  meat. 

Among  the  small  animals  we  will  cite  the  guinea-pig,  which  ha-  a 
pronounced  receptivity.  The  rabbit  is  far  less  sensitive  than  the 
guinea-pig.  With  the  various  species  of  mammalia,  inoculation 
into  the  nerve  centres  offers  a  very  sure  procedure  for  communicating 
glanders.  Success  is  thus  obtained,  even  with  refractory  animal-: 
while  in  those  which  are  susceptible,  a  disease  with  a  particularly 
grave  and  rapid  evolution  appears,  and  the  virulence  of  the  bacillus 
is  found  to  be  exalted. 

Birds  are  very  slightly  sensitive  to  glanders:  they  might  even  be 
said  to  be  refractory,  excepting  the  pigeon,  the  immunity  of  which 
is  incomplete. 

Etiology.  It  was  for  a  long  time  admitted  that  glanders  may 
originate  spontaneously,  at  least  in  the  horse.  At  present  it  is  known 
that  this  disease  cannot  occur  except  by  contagion,  either  through 
direct  inoculation,  or  through  infection.  It  is,  nevertheless,  certain 
that  a  predisposition  is  created  by  a  great  many  causes — fatigue, 
bad  nourishment,  defective  hygiene,  etc. 

Man  hardly  ever  contracts  the  disease  from  any  other  animal 
than  the  horse:  it  is,  therefore,  conceivable  that  it  should  be  rare 
among  women;  of  the  latter  sex  Bollinger  finds  only  6  out  of  a  total 
of  120  cases. 

Since  glandered  horses  are  now  being  slaughtered,  the  frequency 
of  the  disease  has  been  rapidly  declining.  The  persons  affected 
are  naturally  those  working  about  horses — hostlers,  veterinarians, 
farmers,  and  the  like. 


270  INFECTIOUS  DISEASES. 

In  some  instances  the  disease  has  been  communicated  by  biting 
(H.  Landouzy).  The  result  is  not  always  positive,  and  everyone 
remembers  that  CI.  Bernard  experienced  no  disturbance  after  being- 
bitten  by  a  glandered  horse  in  the  course  of  his  experiments. 

It  has  even  been  admitted  that  the  virus  at  times  may  penetrate 
through  the  intact  skin.  The  experiments  of  Babes  tend  to  support 
this  view.  This  author  has  seen  a  few  guinea-pigs  contract  the 
disease  after  a  salve  containing  virulent  bacilli  was  rubbed  into  the 
healthy  skin.  Penetration  is  effected  through  the  cutaneous  glands. 
Arrazat  reported  an  observation  in  which  glanders  caused  death 
in  ten  days,  and  no  wound  of  inoculation  was  discoverable.  It 
follows  from  Nocard's  investigations,  however,  that  the  absolutely 
healthy  skin  does  not  allow  penetration — rubbing  practised  upon 
three  asses  remained  ineffective.  Operating  in  the  same  manner 
upon  fifteen  guinea-pigs,  this  author  found  that  only  two  contracted 
the  disease,  which  latter  result  he  attributes  to  the  presence  of  such 
abrasions  as  may  easily  escape  detection. 

The  mucous  membranes  may  similarly  serve  as  routes  of  pene- 
tration. There  are  on  record  several  observations  in  which  horse- 
shoers  contracted  the  malady  by  drinking  from  the  same  pail  as 
their  horses,  or  wiping  their  noses  with  the  rag  which  had  been  used 
to  cleanse  the  nostrils  of  the  diseased  animals. 

The  ingestion  of  infected  flesh  has  communicated  the  disease,  the 
bacilli  penetrating  through  the  buccal  or  intestinal  mucous  mem- 
branes. Bollinger  affirms  that  the  respiratory  apparatus  is  another 
portal  of  entrance,  especially  in  those  cases  in  which  general  symp- 
toms precede  local  manifestations. 

Pathological  Anatomy.  The  granulation  of  glanders  occupies  an 
intermediate  position  between  suppuration  and  tubercle.  In  acute 
cases  it  resembles  rather  suppurating  lesions;  in  chronic  cases  it  is 
analogous  to  tubercular  lesions. 

The  histological  study  of  glanders  has  chiefly  been  made  upon 
lesions  experimentally  produced.  The  best  descriptions  are  those 
given  by  Baumgarten,  Leclainche  and  Moutane,1  and,  above  all, 
by  Lereclcle.2  The  first  phenomenon  is  represented  by  an  intra- 
vascular accumulation  of  polynuclear  leucocytes;  the  latter  seize 
upon  the  bacilli  and  arrive  in  such  large  numbers  that  they  obstruct 

1  Leclainche  and  Moutand.  Etude  sur  l'anatomie  pathologique  de  la  morve  pul- 
monale.   Annales  de  l'lnstitut  Pasteur,  1893. 

Leredde.     Etude  sur  l'anatomie  patholog.  de  la  morve.     These  de  Paris,  1893. 


NODULAR  INFECTIONS.  277 

the  capillaries  in  which  they  accumulate.  Thu  i  con  tituted  an 
embryonal  nodule.  The  cells  then  undergo  degeneration,  their 
nuclei  break  up,  and  their  protopla  im  become  ca  eou  ,  The  bacilli 
iJuis  liberated  are  taken  up  by  Hie  vascular  endothelial  cells,  which 
heroine  tumefiei i.  [f  die  evolution  continue  .  Du •••'■  leucoc 
assemble  around  the  central  caseous  mass. 

In  chronic  cases  mononuclear  leucocytes  take  pari  in  theproc 
A  sclerotic  tissue  develops  which  may  be  composed  of  small,  caseouf 
masses  and  giani  cells  formed  a1  the  expense  of  mononuclear  leuco- 
cytes.   Owing  to  these  cells,  the  histological  constitution  of  the 
lesion  resembles  the  tubercular  process. 

This  brief  description  shows  thai  the  nodule  of  glanders  us  essen- 
tially formed  of  wandering  cells:  first,  polynuclear;  subsequently, 
mononuclear.  Contrary  to  the  opinion  of  Baumgarten,who  attributed 
to  them  the  main  role,  the  fixed  cells  of  the  tissues  play  a  very 
limited  part  in  the  process. 

Tuberculosis. 

The  definition  of  tuberculosis1  is  at  present  furnished  by  the 
pathogenic  conception.  It  is  the  disease,  or  rather  all  the  lesion-, 
produced  by  Koch's  bacillus.  The  knowledge  of  the  pathogenic 
agent  has  made  it  possible  to  trace  a  series  of  apparently  dissimilar 
manifestations  to  their  true  cause  and  to  demonstrate  the  relation- 
ship existing  between  the  tuberculosis  of  man  and  that  of  animals. 

Biology  of  the  Bacillus.  It  is  difficult  to  obtain  a  first  culture  of 
tubercle  bacillus.  Either  the  organs  of  a  guinea-pig  inoculated  with 
human  tuberculosis  are  taken  as  a  point  of  departure,  or,  as  Koch 
and  Kitasato  have  proposed,  a  particle  from  the  central  portion  of 
a  mass  of  sputum  is  used.  The  cultures  grow  better  in  gelatinized 
serum  than  in  any  other  medium.  At  the  end  of  ten  or  fifteen 
days  colonies  appear  which  soon  assume  the  form  of  well-isolated, 
whitish  or  yellowish  masses,  composed  of  dry.  roughened  pellicles. 
In  successive  cultures  the  masses  coalesce  to  form  dense  and  thick 
membranes. 

The  tubercle  bacillus  is  affected  in  a  peculiar  way  by  coloring 
substances.  Everyone  knows  the  procedure  of  Ehrlieh  which 
enables  us  to  distinguish  this  bacillus  from  all  other  microbes  except 

1  Tuberculosis,  tubercle:  Latin,  (uberculum,  derived  from  tuber,  tumor.  Both  tuber 
and  tumor  are  formed  from  the  Sanscrit  radical  tu.  to  grow. 


278  INFECTIOUS  DISEASES. 

that  of  leprosy.  This  procedure  has  undergone  many  modifications; 
all  the  proposed  methods,  however,  are  based  upon  the  following 
fact — the  microbe  is  with  difficulty  impregnated  by  the  aniline  dyes, 
but  once  the  dyes  penetrate  it  retains  them  powerfully  and  resists 
decolorization  by  dilute  acids. 

The  bacillus  appears  in  the  form  of  small  rods,  usually  measuring 
from  3,u  to  4,«  in  length  and  0.3  ^  to  0.5/;  in  breadth;  they  are 
straight  or  slightly  bent,  at  times  assuming  the  shape  of  an  S,  or 
curved  at  one  extremity.  Their  protoplasm  is  sometimes  homo- 
geneous, at  other  times  formed  of  small  ovoid  or  round  grains. 
In  their  interior  are  often  observed  colorless,  oval  vacuoles  which 
have,  it  seems,  sometimes  been  mistaken  for  spores. 

Until  recently  the  agent  of  tuberculosis  had  been  classed  among 
the  bacilli.  In  1884,  Petrone,  impressed  by  certain  morphological 
characters  of  the  microbe,  thought  that  it  should  be  classed  between 
the  micromyces  and  schizomyces.  This  opinion  attracted  no  atten- 
tion. Metchnikoff  showed,  however,  that  the  bacillus  sometimes 
presents  elongated,  filamentous  forms  bearing  terminal  or  lateral 
enlargements.  He  finally  pointed  out  the  important  fact  that  the 
filaments  may  be  divided.  Maffucci  argued  that  these  various 
phenomena  are  observed  only  in  cultures  of  avian  origin;  and  this 
was  then  employed  as  an  argument  in  support  of  the  dualistic  theory 
of  tuberculosis.  It  is  at  present  known  that  the  same  forms,  though 
with  some  difficulty,  may  be  obtained  with  human  tuberculosis, 
and,  according  to  recent  investigations,  it  seems  certain  that  the 
bacillary  form  of  Koch's  microbe  is  but  a  temporary,  transitional 
one,  and  that  this  parasite  must  be  looked  upon  as  a  plant  of  rela- 
tively higher  development,  belonging,  with  the  actinomyces,  to  the 
group  of  streptothrixge  or  oospora.  It  would,  therefore,  deserve 
the  name  oospora  kochii  or  tuberculomyces  (C.  Jones);  it  might 
be  called  tuberculomyces  hominis  or  T.  avium,1  according  as  the 
microbe  is  of  human  or  avian  origin. 

It  is  not  simply  for  theoretical  interest  that  we  dwell  upon  these 
results ;  they  enable  us  to  correlate  various  pathogenic  agents  which 
arouse  comparable  reactions  in  the  organism.  In  fact,  clinical  ex- 
perience had  beyond  all  doubt  recognized  the  relationship  between 
actinomycosis  and  tuberculosis;  it  is,  therefore,  important  to  point 

1  Coppen  Jones.  Ueber  die  Morphologie  unci  systematische  Stellung  der  Tuberkelpilzes. 
Centralb.  f .  Bakt.,  Bd.  xvii.,  1895.  Ueber  die  Nomenklatur  der  sog.  Tuberkelbacillus, 
ibid.,  1896,  Bd.  xx. 


NODULAR  INFECTIONS.  279 

out  that  their  pathogenic  agents  belong  to  closely  allied  botai 

species. 

The  tubercle  bacillus  pre  ents  a  very  strong  resistance  to  various 
destructive  agents.  When  dried,  i1  preserves  for  a  long  time  ite 
noxious  properties,  especially  when  the  surrounding  temperature  i- 
low.  Thus,  according  to  Pietro,  i1  remains  virulenl  for  nine  or  ten 
months  at  77°  V.  (25°  C),  for  two  months  al  86°  or  95°  I  ,  30°  or 
:tf°  C),  "'"'(I  for  one  month  al   L22°  I'.  (50°  ' 

According  to  Cadeac  and  Mallet,  fragments  of  tubercular  lung 
buried  for  one  hundred  and  sixty-seven  days  produced  tuberculosis 
when  they  were  inoculated  into  animals;  beyond  this  period  they 
gave  rise  to  septicemia;  pieces  of  the  same  organ  Left  in  water  had 
not  yet  lost:  their  virulence  a1  the  end  of  one  hundred  and  twenty 
days. 

The  tubercle  bacillus  is  rather  sensitive  to  the  effect  of  heat;  il 
is  killed  by  ebullition  of  a  few  minutes;  when  dried,  it  does  not 
resist  the  action  of  hot -water  vapor.  According  to  Galtier,  however, 
it-  can  endure  a  temperature  of  140°  F.  (60°  C.)  for  twenty  minutes, 
and  one  of  158°  F.  (70°  C.)  for  ten  minutes.  Ebullition  kills  it 
in  five  minutes  (Sormani).  The  rays  of  the  sun  exerl  the  most 
destructive  influence  and  kill  it  most  rapidly  (Koch). 

Etiology.  The  contagium  of  tuberculosis  may  be  transmitted 
from  animals  to  man,  from  man  to  animals,  from  animal  to  animal, 
and  from  man  to  man. 

The  contamination  of  man  by  animals  raises  several  problems  of 
interest.  In  fact,  it  must  first  be  questioned  whether  tuberculosis 
is  similar  in  all  the  animal  species.  If  such  is  the  case,  as  is  now 
generally  admitted,  is  it  dangerous  for  man  to  ingest  the  flesh, 
viscera,  milk,  and  other  products  of  tubercular  animals?  The 
muscles  seem  to  have  very  little,  if  any,  virulence.  The  milk,  as 
has  already  been  stated,  seldom  contains  bacilli,  except  in  cases 
of  mammary  tuberculosis.  This  source  of  danger,  therefore, 
although  real,  is  not  so  great  as  was  once  believed,  since  mammary 
tuberculosis  is  rare.  Bang  has  observed  only  seven  cases  of  mam- 
mary tuberculosis  in  Copenhagen  in  the  course  of  a  year :  in  France 
it  seems  to  be  still  less  frequent. 

Among  the  products  which  are  said  to  have  transmitted  tuber- 
culosis, we  may  mention  vaccine  lymph.  Since  animal  vaccination 
has  come  into  universal  use  the  question  has  acquired  particular 
interest,  the  more  so  since  Toussaint  succeeded  in  inoculating  tuber- 


280  IM-ECTIOUS  DISEASES. 

culosis  through  the  agency  of  this  fluid.  This  result  has  not  been 
confirmed,  and  the  experiments  of  Lothar-Mayer,  Straus,  Chauveau, 
Josserand,  and  Nocard  demonstrated  that  the  bacillus  is  not  found 
in  the  vaccinal  fluid  of  either  bovidae  or  man. 

Finally,  the  dissemination  of  the  bacillus  through  the  urine  of 
dogs  must  be  taken  into  account.  Tuberculosis,  which  is  not  rare 
among  these  animals,  often  involves  the  kidneys,  and,  in  this  case, 
the  agent  passes  into  the  urinary  secretion. 

The  transmission  of  tuberculosis  of  man  to  animals  has  been 
demonstrated  by  a  great  number  of  examples. 

House  animals  such  as  dogs,  cats,  birds  and,  notably,  parrots  are 
usually  contaminated. 

That  transmission  of  tuberculosis  does  occur  from  man  to  man 
and  between  animals  of  the  same  species  is  a  truth  demonstrated 
beyond  all  possible  doubt. 

Flies  ma}*  carry  tubercle  bacilli  (Spillmann  and  Haushalter),  but 
they  disseminate  rather  than  directly  inoculate  the  virus.  The 
bacilli  may  likewise  remain  virulent  for  a  long  period  in  the  interior 
of  earth-worms  (Lortet  and  Despeignes). 

Pathological  Anatomy.  Tubercular  lesions  assume  two  principal 
forms:  they  may  appear  in  the  form  of  granulations,  which  are 
peculiarly  characteristic  when  examined  in  the  serous  membranes. 
They  are  small,  hard,  non-enucleable  nodules,  often  surrounded  by 
a  red,  vascular  zone.  Their  size  varies  from  0.5  mm.  to  2  or  3  mm. ; 
they  are  at  first  translucent,  but  subsequently  become  opaque  and 
yellowish  at  their  centres.  They  sometimes  present  rounded,  gray 
or  yellow,  isolated  masses  the  size  of  a  pea,  a  hazelnut,  or  even  a 
walnut  (Laennec's  tubercles),  or  they  may  form  opaque  deposits 
infiltrating  the  tissues  (caseous  masses).  In  both  instances  the 
lesion  is  essentially  composed  of  granulations  which  cannot  be 
recognized  with  the  unaided  eye. 

Alongside  with  these  two  principal  types  must  be  placed  certain 
alterations  which,  at  first  sight,  appear  absolutely  different.  Many 
scrofulides,  cold  abscesses,  lupuses,  synovitis  with  riziform  grains 
are  of  tubercular  nature.  The  same  is  true  of  certain  cases  of 
pleurisy,  although  examination  of  the  lungs  does  not  seem  to  reveal 
the  presence  of  any  specific  lesions. 

It  may  then  be  asked  on  what  ground  are  such  morbid  manifes- 
tations held  to  be  tubercular?  At  the  present  day,  the  presence  of 
Koch's  bacillus  seems  to  be  sufficient  to  affirm  the  nature  of  the 


UODXJLAR   INFECTIONS.  2*\ 


alteration.  For  some  time  past,  however,  histological  inve  tigatiom 
have  considerably  extended  the  domain  of  tuberculo  i  ,  The 
criterium  is  no  longer  the  tubercular  corpuscle  of  Lebert,  bul  the 
presence  of  a  gianl  cell  or  a  peculiar  arrangemenl  of  various  cellfl 
designated  under  the  name  elementary  tubercle  or  tubercular  follicle. 
No  doubt  the  specific  character  of  this  lesion  i-  qo1  absolute,  and 
more  or  less  similar  alterations  may  be  encountered  where  there 
is  no  tubercular  infection.  Nevertheless  rnicroscopiste  must  be 
credited  with  having  supplied  a  powerful  argumenl  in  aupporl  of 
the  unity  of  tuberculosis  and  having  included  with  this  di 
diverse  lesions  whirl)  really  belonged  therein. 


I    [Q      6 


kCi<^v, 


T^mmPJ.  i  ' 


Schematic  tubercular  follicle,  showing  the  three  classical  zones  and  the 
distribution  of  bacilli. 

Let  us,  therefore,  investigate  the  constitution  of  a  tubercular 
follicle,  and,  to  this  end,  let  us  suppose  an  ideal  elementary  tubercle, 
ignoring  the  tissue  in  which  it  has  developed  and  the  surrounding 
alterations  which  it  may  have  produced. 

What  peculiarly  characterizes  the  tubercular  follicle  is  not  such  or 
such  cellular  elements,  but  the  mutual  arrangement  of  the  various 
elements  of  which  it  is  composed. 

Theoretically,  according  to  the  conception  of  Koster,  Schuppel, 
and  Friedlaender,  the  tubercular  follicle  is  formed  of  three  zones 
(Fig.  6)  at  the  centre,  a  giant  cell,  the  RiesenzeUe  of  German 
authors;  around  it,  epithelioid  cells,  and  at  the  periphery  an  area 
of  embrvonal  cells. 


282  IXFECTIOUS  DISEASES. 

The  giant  cell,  held  by  Schuppel  to  be  characteristic,  is  composed 
of  a  mass  of  protoplasm  containing  twenty,  or  thirty,  or  more  nuclei, 
situated  at  the  periphery  of  the  cell,  where  they  form  a  crown  or  a 
crescent.  The  cell  itself  is  rounded,  irregular,  flat  or  spherical  in 
shape,  often  provided  with  ramified  prolongations.  The  nuclei  of 
the  giant  cells  are  commonly  oval  and  nucleolated;  in  some  cases 
they  are  elongated  and  sinuous,  or  may  even  present  the  form  of 
a  Z.  Finally,  when  greatly  magnified,  there  may  be  seen  in  some 
of  the  cells  karyokinetic  figures  in  connection  with  indirect  division 
of  the  nuclei.  The  aspect  of  the  nuclei  and  their  arrangement  in  the 
form  of  a  peripheral  crown  enables  one  to  differentiate  the  tuber- 
cular giant  cell  from  myeloplaxes  and  sarcomatous  giant  cells. 

The  middle  zone  is  composed  of  large  epithelioid  cells ;  the  nuclei 
are  rounded  or  oval,  and  the  protoplasm  is  abundant  and  somewhat 
granular.  These  cells  often  contain  one,  two,  or  more  bacilli;  they 
seem  to  perish  when  the  parasites  become  more  numerous. 

The  peripheral  cells  are  simple  embryonal  cells,  presenting  nothing 
particular.  They  are  very  numerous  and  pressed  one  against 
another.  They  appear  in  the  form  of  rounded  elements,  measuring 
4«  to  9,«,  and  are  remarkable  for  the  large  size  of  their  nuclei  and 
the  scantiness  of  their  protoplasm.  In  the  midst  of  these  cells  are 
found  a  few  fusiform  elements  which  represent  a  more  advanced 
stage  of  cellular  development. 

The  elementary  follicle  is  not  always  constituted  in  such  a  perfect 
maimer  as  above  described.  At  the  beginning  of  the  process  all 
that  is  found  is  a  collection  of  round  cells;  at  a  more  advanced 
period  the  epithelioid  cells  maybe  wanting  and  the  lesion  may  consist 
simply  of  a  giant  cell  surrounded  by  embryonal  elements. 

The  tubercle  is  a  non-vascular  production.  This  is  a  feature  of 
great  importance.  At  the  start,  while  there  is  nothing  but  a  simple 
mass  of  cells,  some  permeable  vessels  may  yet  be  found;  but  subse- 
quently they  become  obliterated  and  disappear;  their  lumina  are 
occupied  by  a  granular  coagulum  of  fibrin,  imprisoning  in  its  meshes 
white  corpuscles  accumulated  along  the  inner  walls.  This  vascular 
obliteration  has  been  variously  explained.  Some  authors  have 
assumed  a  compression  of  the  vessel  (Rindfleisch),  others  a  coagu- 
lation of  the  blood  (Chauveau) ,  and  still  others  a  primary  alteration 
of  the  wall — an  endocapillaritis  (H.  Martin). 

About  the  irritated  point  the  vessels  dilate  and  send  out  prolonga- 
tions, which  are  but  short-lived. 


NODULA  i:  INFECTIONS. 

Histogenesis  of  Tubercle.  The  method  of  inv<  ligation  ; 
been  quite  differenl  before  and  since  Koch's  discovery.  During 
the  period  thai  may  be  designated  as  prebacterial,  very  exacl  and 
detailed  descriptions  were  given  of  the  pathological  anatomy  of  the 
tubercle.  When  the  specific  germ  of  the  di  ea  e  wag  known  and 
cultivated  it  became  possible,  by  inoculating  it  into  animal 
observe  day  after  day  the  development  of  the  tubercular  neoplasm, 
without  running  the  risk  of  regarding  accessory  and  secondary 
processes  as  essential,  or  considering  as  specific  such  alterations  ae 
are  common  to  other  diseases. 

The  importance  of  lymphatic  elements  in  the  genesis  and  constitu- 
tion of  tubercle  was  noted  from  the  very  beginning  of  researches. 
Virchow  and  his  disciples  class  it  with  lymphomata.  Klebs  and 
Koster  think  it  takes  origin  in  the  lymphatic  capillary  network-. 
Wagner  emphasizes  its  structural  analogy  to  lymphatic  glands 
(cytogenic  tuberculosis).  H.  Martin  and  Kiener  compare  it  to  the 
milky  patches  of  (lie  omentum. 

Histologists  sought  for  a  specific  element  thai  would  enable  them 
to  distinguish  tubercle  from  similar  neoplasms;  and  such  were 
thought  to  be  the  giant  cells  and  the  absence  of  vessels  in  the  tubercle. 

It  was  not  long,  however,  before  new  contributions  demonstrated 
that  giant  and  epithelioid  cells  are  in  nowise  specific.  Heidenhain, 
Weiss,  Baumgarten,  and  Ziegler  produced  these  elements  by  insert- 
ing foreign  bodies  into  the  subcutaneous  cellular  tissue.  Laulanie 
observed  in  the  cat  granulations  which  presented  the  appearance 
and  structure  of  tubercle  and  were  caused  by  the  strongylus  vasorum, 
Hip.  Martin  produced  pulmonary  granulations  by  intravenous 
inoculation  of  inert  powders. 

While  discussing  the  diagnostic  value  of  giant  and  epithelioid 
cells,  the  authorities  endeavored  to  discover  the  mode  of  formation 
of  these  elements.  Langhans  suggested  two  possible  events:  either 
the  giant  cell  develops  at  the  expense  of  one  altered  cell,  or  is  formed 
by  the  union  and  confluence  of  several.  According  to  Koster,  it 
results  from  the  proliferation  of  the  vascular  endothelium :  according 
to  Ziegler  it  develops  at  the  expense  of  leucocytes,  while  Shuppel 
holds  it  to  be  due  to  the  hypertrophy  of  one  migrated  white  corpuscle 
followed  by  alterations  in  the  bloodvessels.  This  vascular  origin, 
while  admitted  by  Cornil,  was  doubted  by  Malassez.  Charcot  and 
Gombault  contended  that  the  giant  cell  resulted  from  fusion  of 
manv. 


284  INFECTIOUS  DISEASES. 

Such  were  the  opinions  of  authors  concerning  the  histogenesis  of 
tubercle  when,  in  1882,  the  discovery  of  the  tubercle  bacillus  by 
Koch  brought  accuracy  to  our  knowledge  of  tuberculosis.  The 
specific  element,  which  pathological  anatomy  had  failed  to  furnish, 
was  found  out  by  bacteriology. 

From  that  moment  two  principal  theories  have  been  advanced. 
According  to  some,  the  tubercular  neoplasm  is  composed  solely  of 
cells  that  pass  out  of  the  vessels  to  ingest  the  bacilli;  the  tubercle 
is  a  superadded  production  developing  at  the  expense  of  protective 
cells  that  are  attracted  toward  the  point  attacked.  Others  assert 
that  it  is  formed  of  the  constituent  cells  of  tissues  (epithelial  cells, 
fixed  cells  of  connective  tissues,  vascular  endothelium,  etc.),  and 
that  it  is  to  be  attributed  to  the  transformation  of  pre-existing 
elements  normal  to  the  parts. 

Among  the  advocates  of  the  former  theory  is  Koch.  The  bacillus 
ingested  by  the  wandering  cell  is  transported  by  it  into  the  organs, 
and  Koch  is  not  far  from  believing  that  the  same  cells  give  origin  to 
both  the  epithelioid  and  giant  cells.  While  Koch  hesitates,  Metchni- 
koff  is  positive.  According  to  the  latter  authority,  the  phagocytes 
pick  up  and  digest  the  tubercle  bacillus.  Moreover,  the  giant  and 
epithelioid  cells  which  he  studied  in  a  small  rodent,  the  spermophile, 
into  which  he  inoculated  avian  tuberculosis,  also  have  phagocytic 
properties.  The  latter  statement  is  contested  by  a  number  of 
authorities.  Gilbert  and  Girode,  as  well  as  Yersin  subsequently 
proved  that  tubercle  develops  at  the  expense  of  wandering  cells. 
Borrel,  studying  the  histogenesis  of  tubercle  in  the  lung  and  kidney 
by  means  of  inoculations  of  cultures  of  human  tuberculosis,  saw  the 
bacilli  ingested  by  polynuclear  leucocytes :  the  latter,  however,  died 
rapidly  and  were  replaced  by  mononuclear  leucocytes  which  in  their 
turn  seized  upon  the  bacilli  and  were  transformed  into  epithelioid 
and  giant  cells.  Josue,  inoculating  cultures  of  human  or  avian 
tuberculosis  into  the  bone-marrow  of  rabbits,  discovered  the  same 
process  and  created  in  this  animal  lesions  which  are  circumscribed 
in  the  case  of  human  and  diffuse  in  that  of  avian  tuberculosis. 

The  advocates  of  the  formation  of  tubercle  at  the  expense  of  the 
fixed  cells  of  tissues  are  also  supported  by  experimental  investiga- 
tions. Baumgarten,  who  is  an  enthusiastic  defender  of  this  theory, 
inoculated  fragments  of  tubercular  substance  into  the  anterior  cham- 
ber of  the  eye  of  a  rabbit,  and  saw  the  fixed  cells  divide  by  karyo- 
kinesis,  giving  rise  to  epithelioid  and  giant  cells.     The  intervention 


NODULA  i:  TNFECTI0N8. 

of  the  leucocytes  is  secondary;  they  invade  the  neoplasm  already 
constituted  by  the  elements  which  originate  by  indirect  division  from 
the  pre-existing  tissue  cells.  Tubercle  Is  formed  in  all  organs  in  a 
similar  manner.     Baumgarten,  who  reject*  phagocyto  i  thai 

the  bacilli  are  not  ingested  by  the  cells.  Kostenitch,  Vblkow,  and 
Straus  are  also  advocates  of  the  theory  of  the  formation  of  tubercle 

at  I  he  expense  of  fixed  cells. 

As  to  the  gianl  cell,  ii  is  believed  by  some  to  I"-  formed  of  one 
cell.     Under  the  influence  of  an  irritation  too  weak  to  bring  about 

its  division,  its  nuclei  proliferate  and  remain  enclosed  in  Hie  hyper- 
trophied  and  undivided  protoplasm  (Koch,  Weigert,  Baumgarten). 

Others  contend  l lint  the  gianl  cell  is  produced  by  the  coalescence  of 
several  cells,  or  by  the  penetration  of  leucocytes  into  the  mass* 
degenerated  protoplasm,  or  by  these  two  processes  simultaneously 

(Arnold,  Yersin,  Borrel,  Kostenitch  and  Volkow.  Josu6). 

We  are  thus  confronted  by  two  theories  as  to  the  histogenesi 
tubercle;  both  are  supported  by  well-observed  experimental  : 
It  is  therefore  to  be  assumed  that  both  contain  some  truth  and  it  may 
then  be  asked  whether  they  cannot  be  harmonized.  Josue*  remarks 
that,  under  the  name  of  fixed  tissue  cells,  some  have  confounded  the 
fixed  cells  of  connective  tissue,  which  certainly  play  a  phagocytic  role. 
and  the  epithelial  cells.  In  his  opinion,  the  mesodermic  cells — the 
leucocytes,  the  fixed  cells  of  connective  tissue — ingest  the  bacilli, 
but  the  toxins  secreted  b}^  the  microbes  may  act  upon  the  surround- 
ing epithelial  cells  and  produce  in  them  epithelioid  degeneration. 
Accordingly,  from  a  histological  standpoint,  all  cells  participate  in 
the  formation  of  tubercle ;  but  as  far  as  the  fight  against  the  invading 
germ  is  concerned,  the  principal  role  devolves  upon  the  mesodermic 
cells. 

On  the  arrival  of  the  bacillus,  polynuclear  leucocytes  undertake 
to  ingest  it,  but  they  rapidly  perish.  Then  mononuclear  leucocytes 
and  connective  tissue  cells  seize  upon  the  germ.  Two  events  are 
then  possible.  The  organism  may  immediately  triumph,  and  the 
tubercle  is  not  produced,  or  the  bacillus  maybe  victorious,  and  then 
two  successive  phases  supervene:  in  the  first,  the  cells  are  trans- 
formed into  epithelioid  elements  and  a  tubercle  is  produced :  in  the 
second  phase,  the  tubercle  undergoes  caseous  degeneration.  Even 
at  this  stage  of  evolution  the  organism  may  triumph :  if  the  numerous 
leucocytes  surrounding  or  penetrating  the  focus  remain  powerless, 
there  is  another  process  capable  of  circumscribing  the  lesion  and  of 


286  IXFECTIO  US  DISEASES. 

killing  the  bacillus  imprisoned  in  the  products  of  its  own  creation — 
viz.,  the  process  o(  sclerosis  mvadihg  the  tubercle. 
Thus  far  we  have  dealt  with  the  local  manifestations  of  the  bacillus. 

Its  action  is  not.  however,  limited  to  the  point  at  which  it  comes  in 
contact  with  the  tissue  cells,  as  may  be  proved  by  a  study  of  the 
modifications  occurring  in  the  marrow  of  bones  in  the  absence  of  all 
osteomedullary  localization.  In  fact,  Josue  has  recognized  that 
when  tubercular  lesions  exist  at  any  point  of  the  organism  a  profuse 
cellular  proliferation  occurs  in  the  bone  marrow.  The  modifications 
of  this  tissue,  with  reference  to  the  defense  of  the  organism,  are 
equally  observed  in  man  and  in  rabbits  which  have  been  inoculated 
in  regions  far  from  bones  or  subjected  to  subcutaneous  injections 
of  tuberculin. 

Evolution  of  Tubercle.  After  having  studied  the  structure  and 
mode  of  formation  of  the  elementary  follicle,  it  is  easy  to  comprehend 
the  development  of  granulations,  of  tubercles  properly  so  called,  and 
of  caseous  masses. 

Gray  granulation  is  commonly  formed  of  several  tubercular  fol- 
licles. Wagner  and  Charcot  admit,  in  complex  follicles,  as  many 
simple  follicles  as  there  are  giant  cells.  Tubercles,  properly  so 
called,  which  are  larger  than  gray  granulations,  are  essentially  made 
up  by  the  union  of  several  elementary  tubercles,  but  the  central  part 
undergoes  a  modification  designated  as  caseous  degeneration.  At 
the  periphery  are  found  numerous  embryonal  cells  similar  to  those 
observed  in  the  external  zone  of  the  follicles.  The  middle  zone  is 
remarkable  for  the  presence  of  giant  cells  forming  a  crown  around 
the  central  degenerated  mass.  This  agglomeration,  therefore,  pos- 
sesses a  certain  individuality.  It  does  not  represent,  juxtaposed, 
independent  follicles  each  undergoing  degeneration;  we  are  in  the 
presence  of  a  true  pathological  unity  the  centre  of  which  degen- 
erates. 

The  foregoing  statement  with  regard  to  tubercle  may  be  applied 
to  tubercular  infiltration,  which  is  characterized  by  confluent  granu- 
lations connected  by  means  of  embryonal  cells.  According  as  the 
mass  is  made  up  of  granulations  or  of  caseous  tubercles,  the  condition 
is  known  as  gray  or  yellow  infiltration.  As  Prof.  Grancher  states, 
every  tubercle  is  composed  of  two  zones — a  central  caseous  zone  and 
a  peripheral  embryonal  one.  A  closer  study  of  the  evolution  of  the 
lesions  shows  that  a  tubercle  is  liable  to  two  forms  of  degeneration 
— fibrous  and  caseous. 


NODULAR   INFECTIONS. 

Caseification  is  preceded  by  a  Btage  which  Prof.  Grancher  di 
aates  as  vitreous  degeneration:  the  giant  and  epithelioid  cell  lose  their 
nuclei,  become  vitreous,  homogeneou  ,  and  coale  <■<•:  thm  a  translu- 
cent mass  is  formed  with  fii  lire  imparting  to  ii  the  appearance  of 
an  irregular  mosaic.  This  peculiar  substance  look  omewhal  like 
amyloid  substance,  bu1  does  nol  manifest  ite  reactions.  The  trans* 
lucent  mass  soon  becomes  opaque.  This  is  caseous  transformation, 
in  which  cellular  elements  are  no  longer  recognizable;  the  bacilli 
to  share  the  fate  of  the  animal  cells;  there  are  very  few  of  them  to 
be    found.     This   caseous    transformation,    which    has    long   been 

regarded  as  specific,  may  be  wanting  i an  and  particularly  in 

animals.    On   the  other  hand,  LI  may  be  encountered   in  various 
other  pathological  conditions,  notably  in  syphilis. 

The  caseous  mass  softens,  especially  when  it  is  communicating 
with  the  exterior;  it  may  undergo  a  purulenl  transformation,  result- 
ing from  contamination  by  pyogenic  bacteria. 

In  other  instances  the  tubercle  undergoes  a  fibroin  metamor- 
phosis; this  is  a  tendency  toward  recovery.  Tubercle  is  transformed 
into  a  hard  nodule  composed  of  a  homogeneous  fibrous  tissue,  includ- 
ing a  few  atrophied  round  cells.  Vessels  develop  in  the  embryonal 
zone  in  which  giant  cells  are  still  found.  At  certain  points  the 
caseous  substance  becomes  encysted ;  at  times  it  is  absorbed.  Finally, 
tubercle  may  become  infiltrated  with  calcareous  salts  and  undergo 
pigmentary  transformation. 

Action  of  Tubercular  Toxins.  The  tubercle  bacillus  is  capable  not 
only  of  producing  tubercles, but  it  may  likewise  produce  fatty, hyaline 
and  amyloid  degenerations.  The  sclerotic  process  which  it  excites 
may  become  preponderant,  leading  to  cirrhoses,  especially  appre- 
ciable in  the  liver,  and  it  may  be  encountered  in  other  parts  of  the 
organism;  the  author  has  shown  its  occurrence  in  the  muscles,  and 
Dr.  Tessier  has  proved  its  importance  in  connection  with  the  heart. 

The  phenomena  of  degeneration  seem  to  be  due  to  secretory  prod- 
ucts of  the  microbes  (Maffucci,  Grancher).  As  to  the  tubercles,  they 
are  produced  by  a  reaction  of  the  system  against  the  bacillus — i.  c 
the  substances  contained  in  the  body  of  the  bacillus.  The  interven- 
tion of  the  living  micro-organism  is  not  necessary.  The  experiments 
of  Prudden  and  Hodenpyle,  Straus,  Gamaleia,  and  Vissman  demon- 
strate that  injection  of  thick  emulsions  of  dead  cultures  of  tubercle 
bacilli  into  the  veins  of  animals  may  produce  extremely  numerous 
granulations  containing;  dead  bacilli  which  can  be  stained  bv  the 


288  INFECTIOUS  DISEASES. 

usual  methods.  This  necrotuberculosis,  to  use  an  expression  em- 
ployed by  Drs.  Grancher  and  Ledoux-Lebard,  is  characterized  by 
considerable  emaciation  and  a  cachexia  ending  in  death.  The 
necropsy  reveals  tubercular  granulations,  particularly  abundant  in 
the  lungs  and  remarkable  for  their  tendency  to  undergo  fibrous 
transformation  and  for  the  absence  of  caseation.  Straus  and  Gama- 
leia.  however,  have  seen  the* centre  of  such  tubercles  become  caseous, 
as  under  the  influence  of  living  bacilli.  Schweinitz  and  Dorset 
admit  that  the  necrosing  substance  is  a  definite  body  having  the 
formula  C7H10O4,  and  that  it  is  found  in  culture  fluids.  The  bodies 
of  the  bacilli  contain  an  albuminoid  substance  which  is  antagonistic 
to  the  preceding  one;  it  produces  hyperthermia,  while  the  other 
lowers  the  temperature,  and  it  is  sclerogenic  instead  of  being  necro- 
genic. 

A  series  of  experiments  pursued  by  the  author  demonstrate  that 
special  toxic  substances  are  contained  in  the  tubercular  tissue  itself. 
In  most  cases  he  employed  extracts  of  tubercular  glands  of  cattle 
and  dogs  or  the  liver  of  tubercular  guinea-pigs,  either  pure  or  mixed 
with  substances  capable  of  modifying  their  action.  It  was  thus 
learned  that  tubercular  tissues  contain  substances  more  noxious  for 
the  rabbit  than  the  guinea-pig.  The  emaciation  caused  in  the  rabbit 
is  more  pronounced  and  lasts  longer. 

Inoculability  of  Tuberculosis.  There  is  hardly  a  mammalian  alto- 
gether refractory  to  tuberculosis.  Nearly  all  may  contract  it  spon- 
taneously or  by  inoculation.  In  laboratories  the  animals  most  oper- 
ated upon  are  the  rabbit  and  the  guinea-pig.  With  the  latter  animal 
inoculation  is  successful,  no  matter  by  what  route  the  material  is 
introduced — whether  into  the  subcutaneous  cellular  tissue,  the 
pleura,  the  peritoneum,  or  the  anterior  chamber  of  the  eye. 

As  in  the  case  of  other  infections,  the  number  of  bacilli  introduced 
must  be  taken  into  account :  the  greater  the  amount  of  virus  intro- 
duced the  more  rapidly  the  disease  develops. 

The  researches  of  Bollinger  and  Gebharclt  demonstrate  that  dilu- 
tion of  tubercular  substances  may  render  them  inoffensive:  con- 
taminated milk  loses  its  virulence  if  diluted  to  T\-$  or  y^-.  Animals 
resist  when  they  swallow  2  c.cm.  of  tubercular  sputum  diluted  to  \. 
If,  however,  inoculation  is  made  beneath  the  skin  or  into  the  peri- 
toneum, it  must  be  diluted  to  to  0*000  m  order  to  become  inoffensive. 

Hischberger,  Gebharclt,  and  Wissokowicz  have  also  demonstrated 
that  rabbits  resist  amounts  which  are  fatal  for  guinea-pigs;  in  the 


NODULAR   INFECTIONS.  288 

latter  animals  tuberculosis  developi  when  a  particle  ol  putum  con- 
taining 820  bacilli  is  inoculated.  Upon  this  fad  Wissokowicz  b 
his  explanation  of  the  re  nil  obtained  by  inoculating  ubstance* 
taken  from  local  tuberculosis  in  man.  The  reason  why,  in  this 
instance,  rabbits  resisl  while  guinea-pigs  succumb  is,  according  to 
this  author,  not  the  attenuation  of  the  virus  bul  its  dilution;  the 
number  of  bacilli  is  too  small  to  overcome  the  resistance  of  the 
rabbits.  Dr.  Arloing  objects  to  the  assertion  thai  a  certain  number 
of  rabbits  or  guinea-pigs  may  become  diseased  by  the  injection  of 
diluted  bacilli;  if,  however,  the  virus  is  subjected  to  a  temperature 
of  110°  F.  (t)0°  C.)  for  fifteen,  thirty,  or  sixty  minutes,  it  becomes 
attenuated,  and  the  bacilli  are  then  no  longer  able  to  kill  the  rabbit, 
though  I  hey  still  render  guinea-pigs  tuberculous  by  acting  upon  these 
animals  like  the  scrol'ular  virus:  the  latter  virus,  therefore,  repr< 
an  attenuated  tubercular  virus,  a  more  or  less  fixed  rare  0f  Koch's 
bacillus. 

Tuberculosis  of  Animals.  Among  the  animals  mosl  susceptible  to 
the  spontaneous  development  of  tuberculosis  the  bovidse  must  firsl  be 
mentioned.  The  frequency  of  bovine  tuberculosis  varies  according 
to  races  and  countries.  While  rare  in  polar  countries,  tuberculosis 
is  especially  prevalent  in  hot  countries,  notably  in  Italy,  where  it 
presents  the  characters  of  a  veritable  scourge.  Even  in  those 
countries  in  which  tuberculosis  is  most  frequent,  it  is  exceptional 
in  young  animals ;  the  average  for  calves  is  below  1  per  10.000. 

The  tubercular  infection  is  in  some  cases  expressed  by  a  general 
malady  affecting  the  serous  membranes  and  resembling  human  mil- 
iary tuberculosis;  in  other  instances,  by  pulmonary  or  abdominal 
lesions;  lastly,  the  bacilli  may  become  localized  at  a  certain  point 
and  give  rise  to  local  tuberculosis.  Pulmonary  tuberculosis  is 
undoubtedly  the  most  common  form  of  the  disease. 

The  frequency  of  mammary  tuberculosis  has  been  the  subject  of 
much  controversy.  In  less  than  a  year  Bang  observed  seven  cases 
in  Copenhagen.  In  France  it  seems  to  be  of  rare  occurrence,  and 
danger  of  contamination  through  milk  seems  to  be  not  so  great  as 
Mas  once  believed. 

Observations  upon  tuberculosis  in  the  horse  are  not  very  numerous. 
The  lesions  are  sometimes  limited  to  the  organs  of  the  abdominal 
cavity,  occupying  the  viscera  and  glands:  sometimes  they  are  found 
only  in  the  lungs,  and  in  some  instances  they  are  generalized. 

Tuberculosis  in  swine  varies  according  to  the  countries  from  0.1 

19 


•290  [XFECTIO  US  Disj;.  I SKS. 

to  1  per  1000.  These  estimates,  coming  from  the  abattoirs,  are 
probably  below  the  real  figures,  since  the  diseased  animals  grow 
rapidly  thin,  and  are,  therefore  clandestinely  killed  and  sold. 

Contrary  to  the  assertions  of  some  authorities,  tuberculosis  in 
the  goat  and  sheep  is  not  exceptional.  Moreover,  experimentation 
proves  that  the  goat  can  be  rendered  tubercular  the  same  as  other 
animals. 

The  remarkable  researches  of  Cadiot1  have  established  that  tuber- 
culosis is  very  frequent  in  the  dog.  The  contrary  opinion  is  due  to 
the  fact  that,  in  this  animal,  the  lesions  often  appear  in  the  form  of 
neoplastic  productions,  although,  in  some  instances,  they  are  similar 
to  those  commonly  observed  in  man— 1  e.,  pulmonary  cavities  and 
alterations  in  the  urinary  apparatus. 

In  the  cat,  as  in  the  dog,  tuberculosis  may  be  generalized  or 
limited  to  the  organs  of  the  thorax  and  abdomen.  Voluminous 
mesenteric  adenopathies  are  commonly  present,  indicating  that  the 
virus  has  entered  through  the  intestine. 

According  to  the  statistics  of  the  London  Zoological  Gardens, 
monkeys  become  tubercular  in  the  proportion  of  15  per  cent.  The 
infection  invades  particularly  the  lungs  and  the  liver,  subsequently 
involving  the  kidneys,  the  spleen,  and  less  frequently  the  intestine. 
Contrary  to  what  was  formerly  believed,  rabbits  and  guinea-pigs, 
which  are  so  frequently  employed  for  experimental  purposes,  are 
seldom,  if  ever,  spontaneously  affected  by  this  disease.  The  so-called 
spontaneous  tubercles  are  clue  to  cysticercus,  coccidia,  or  to  microbes 
other  than  Koch's  bacillus. 

Tuberculosis  of  the  Gallinae.  Tuberculosis  of  the  gallime  was 
identified  with  that  of  the  mammalia  when  Koch,  Ribbert,  Babes, 
Cornil,  and  Megnin  demonstrated  the  presence  in  them  of  bacilli  pre- 
senting the  same  coloring  reactions  as  the  bacillus  of  the  mammalia. 
Soon  afterward  Drs.  Nocard  and  Roux  cultivated  the  avian  bacillus, 
and  their  cultures  were  employed  in  all  the  laboratories  of  France 
for  experimental  purposes.  The  identity  of  avian  and  mammalian 
tuberculoses  was  accepted  without  much  controvers3r,  since  experi- 
mentation demonstrated  that  avian  tuberculosis  could  be  inoculated 
into  rabbits,  and  several  observations  seemed  to  point  to  the  trans- 
missibility  of  human  tuberculosis  to  birds. 

It  was  not  long,  however,  before  negative  results  were  reported: 

1  Cadiot.     Tuberculose  du  chien,  Paris,  1892,  vol.  i. 


MODULAR   INFECTIONS.  291 

Straus  and  Wurtz1  caused  chickens  and  a  cock  to  swallow  human 
tubercular  sputa  for  from  six  to  twelve  month  ;  the  animal*  re  i 
and  the  necropsies  demonstrated  the  complete  integrity  of  their 
organs.  Maffucci  also  demonstrated  thai  mammalian  tuberculosis 
was  not  transmit  ted  to  the  gallime;  I  wenty  chickens  were  inoculated 
subcutaneously,  by  the  stomach,  lungs,  peritoneum,  and  vein  .  and 
:ill  resisted. 

The  unity  of  tuberculosis  in  the  various  animal  species  wae  thus 
rendered  questionable.  This  doubl  wassharedby  Koch,who,a1  the 
Congress  in  Berlin,  declared  he  had  resumed  the  study  of  the  question 
and  could  tio  longer  completely  identify  the  tuberculosis  of  birds  and 
of  the  mammalia.  From  thai  momenl  a  series  of  contributions 
appeared  which  clearly  demonstrated  the  differential  characters  of 
the  two  forms  of  tuberculosis.  Mention  may  be  made  of  the  numer- 
ous investigations  which  the  author  pursued  with  Drs.  Cadiol  and 
Gilbert,2  (hose  of  Straus  and  Gamaleia,3  and  of  Courmonl  and  Dor/ 

The  fundamental  fact  demonstrated  by  these  experiments  is  one  of 
general  pathology — i.  e.,  that  tuberculosis  may  be  transmitted  from 
one  species  to  another,  but  its  evolution  is  directed  by  the  infected 
organism  itself.  It  is  the  eternal  question  of  the  seed  and  soil.  The 
hepatic  tubercles  of  the  chicken  and  of  the  pheasant,  for  instance, 
are  not  only  distinguished  from  the  hepatic  tubercules  of  the  mam- 
malia, but  they  are  highly  differentiated  among  themselves,  although 
developing  in  so  closely  allied  animal  species.  This  fact  cannot  be 
too  strongly  emphasized,  since  it  strikingly  shows  the  pathological 
particularism  of  animals  and  indicates  the  great  error  of  hastily 
generalizing  conclusions  drawn  from  experiments  made  upon  a  single 
animal  species. 

Comparison  of  the  Tuberculoses  of  the  Mammalia  and  the  Gal- 
linae.     There  are  certainly  numerous  differences  between  the  virus 

1  Straus  and  Wurtz.  Sur  la  resistance  des  poules  a  la  tuberculoso  par  ingestion. 
Congrea  pour  l'etude  de  la  tuberculose,  18SS. 

;  Cadiot,  Gilbert,  and  Roger.  Note  sur  la  tuberculose  des  volailles.  Soc.  de  biologie, 
Oct.  11,  1890.  Xote  sur  l'anatomie  pathologique  de  la  tuberculose  du  foie  chez  la  poulo 
et  le  faisan,  ibid.,  Oct.  IS,  1S90.  Inoculation  aux  gallinaces  de  la  tuberculose  des 
mammiferes,  ibid.,  July  2.5,  1891.  Inoculabilite*  de  la  tuberculose  des  gallinaces  aux 
mammiferes,  ibid.,  Feb.  S.  1S96.  Unieite  des  tuberculoses  humaine  et  aviaire.  ibid.. 
Feb.  S,  1896.  Sur  un  precede  permettant  de  transmettre  la  tuberculose  des  maniniiferes 
aux  gallinaces,  ibid.,  Nov.  19.  1S9S. 

3  Straus  and  Gamaleia.  Recherches  experimentales  sur  la  tuberculose.  Arch,  de 
medecine  expeximentale,  1891.     Straus.  La  tuberculose  et  son  bacille.  Pari*.  1S95. 

4  Courmont  and  Dor.  Tuberculose  aviaire  et  tuberculose  des  mammiferes.  Oongtvs 
pour  l'etude  de  la  tuberculose,  1S91. 


292  TXFECTIO  US  DISK.  I  s]-;s. 

of  the  mammalia  and  that  of  gallinse.  The  avian  bacilli  are  longer 
and  more  granular.  They  develop  more  readily  in  artificial  culture 
media  and  multiply  at  once  in  glycerinated  agar-agar,  while  the 
bacilli  of  human  tuberculosis  cannot  vegetate  in  this  medium  except 
after  having  been  several  times  cultivated  in  serum.  The  avian 
bacillus  vegetates  at  109.4°  F.  (43°  C.)  and  resists  a  temperature  of 
149°  F.  (65°  C.)i  the  human  tubercle  bacillus  ceases  to  develop  at 
105.8°  F.  (41°  C.)  and  dies  at  149°  F.  (65°  C).  An  avian  culture 
ten  months  old  is  living  and  can  yet  be  sown ;  a  human  culture  loses 
its  capacity  to  vegetate  in  six  months  (Maffucci).  Avian  tuber- 
culosis may  be  transmitted  to  chickens;  it  seldom,  if  ever,  causes 
generalized  tuberculosis  in  guinea-pigs,  and,  except  in  certain  rare 
instances  (observation  of  Richet  and  Hericourt),  it  cannot  be  in- 
oculated into  the  dog.  Human  tuberculosis  is  but  exceptionally 
transmitted  to  chickens;  it  almost  invariably  gives  rise  to  gener- 
alized tuberculosis  in  guinea-pigs,  and  is  easily  inoculated  into  the 
dog. 

Such  are  the  differences  existing  between  the  two  viruses,  and  all 
are  of  secondary  importance,  which  does  not  warrant  their  being  con- 
sidered as  two  different  species.  The  general  features  of  the  two 
bacilli  are  the  same,  and  the  reactions  which  they  arouse  in  the  living 
organism  are  similar.  The  morphological  differences  are  likewise  of 
a  secondary  order.  Differences  no  less  notable  are  observed  when 
tubercular  bacilli  present  in  various  individuals  of  the  same  species 
are  compared  with  each  other.  It  is  not  rare  to  find  in  man  some 
bacilli  longer  and  more  granular  than  others. 

Agreement  is  universal  as  to  the  identity  of  the  soluble  products, 
notably  tuberculin,  whatever  their  origin  may  be. 

These  facts  point  to  the  conclusion  that  the  two  tubercular  bacilli 
represent  two  varieties  of  the  same  species.  There  are  undoubtedly 
marked  differences  between  the  two  varieties,  and  it  is  impossible 
to  apply  to  one  the  results  obtained  with  the  other;  hence,  in  order 
to  avoid  confusion,  it  is  always  necessary  to  indicate  the  virus  em- 
ployed. Nevertheless,  in  conjunction  with  distinctive  characters  of 
importance,  we  find  a  common  basis  warranting  the  belief  that  these 
two  pathogenic  agents  are  derived  from  the  same  species:  unity 
of  tuberculosis  of  the  mammalia  and  of  gallinae;  such  seems  to  us 
the  conclusion  suggested  by  the  ensemble  of  facts  thus  far  observed, 
which  will  now  find  fresh  support  in  the  researches  pursued  by  us 
upon  tuberculosis  of  psittaci. 


NODULAR  INFECTIONS. 


293 


Tuberculosis  of  Psittaci. 

Frohner  and  bis  assistant,  Eberlein,  were  the  first  to  draw  atten- 
tion to  the  frequency  of  tuberculosis  in  parrots  and  to  show  thai 
the  disease  commonly  involved  the  skin,  mucous  membranes,  sub- 
cutaneous and  submucous  connective  tissue,  the  articulations,  and 
hones.  Of  700  parrots  broughl  to  the  clinics  of  the  Berlin  School, 
170  were  tubercular    say  25  per  cent. 

The  cases  studied  by  the  author  with   Drs.  Cadiol  and  Gilb 
were  27  in  number.    Of  these,  L5  were  tuberculosis  of  the  -kin.  \) 
of  the  mucous  membranes,  6  boil  i  of  (Ik- skin  and  mucous  membranes. 
The  lesions  are  in  the  greal  majority  of  cases  aboul  the  head.    Pig.  7) 


Fig.  7. 


Tuberculosis  of  the  parrot. 

Iii  the  majority  of  our  observations  the  lesions  presented  such  a 
peculiar  appearance  that  their  nature  could  not  be  recognized  before 
the  employment  of  bacteriological  measures.  The  cutaneous  mani- 
festations differ  altogether  from  those  observed  in  other  animals; 
they  may  be  compared  only  to  certain  forms  of  lupus  verruc  - 
There  first  occurs  a  shedding  of  the  plumage :  then  the  skin  thickens 
and  becomes  verrucous,  and  vegetations  soon  appear  which  become 
covered  with  thick  crusts.  If  these  be  detached  a  granular  tissue 
is  exposed.     Ulcerations  are  not  uncommon,  and  are  produced  i  -     - 


1  Cadiot,  Gilbert,  and  Roger.  Inoculabilitc  de  la  tuberculose  des  manimiferes  aux 
psittaces.  Soc.  de  biologie,  December  14.  1S95.  La  tuberculose  des  perroquets.  ses  rap- 
ports avec  la  tuberculose  humaine.     La  presse  medicale,  January  26,  1896. 


294  I  NFEi  ■  TIO  US  DISEA  SES. 

dally  when  the  diseased  parts  are  exposed  to  traumatism  or  repeated 
friction.    In  certain  instances  the  lesion  occupies  the  subcutaneous 

tissue;  it  is  a  tumor  of  fibrous  consistency  which  may  attain  the  size 
of  a  cherry.  Later  on  the  centre  softens  and  is  transformed  into  a 
caseous  mass.' 

Finally,  there  is  a  very  peculiar  localization  which  has  given  rise 
to  many  diagnostic  errors.  The  author  refers  to  the  tubercles  devel- 
oping near  the  claws,  which  become  deformed  and  crooked  absolutely 
as  in  the  cases  described  under  the  name  of  gout  of  birds.1 

Visceral  manifestations  with  or  without  other  lesions  may  occur 
— gastroenteritis  marked  by  diarrhea,  and  pulmonary  tuberculosis 
attended  by  a  troublesome  and  frequent  cough. 

As  parrots  live  with  man  and  have  hardly  any  communication 
with  other  animals,  it  is  reasonable  to  assume  that  their  tuberculosis 
is  of  human  origin.  That  is  precisely  what  observations  prove.  In 
a  fair  proportion  of  the  cases  observed  by  us  the  tubercular  parrots 
belonged  to  emaciated  individuals  with  chronic  cough,  the  nature  of 
the  affection  proving  to  be  tubercular  in  certain  cases  which  we  sub- 
mitted to  bacteriological  examination. 

"Without  dwelling  upon  the  inoculability  of  tuberculosis  of  both 
mammalia  and  gallina?  into  the  psittaci,  as  our  experiments  fully 
demonstrated,  we  may  say,  in  conclusion,  that  the  results  obtained 
with  the  avian  virus  are  altogether  comparable  to  those  furnished 
with  the  human  virus.  The  parrot,  among  birds,  behaves  as  does 
the  rabbit  among  mammalia.  These  are  two  animals  equally  sensi- 
tive to  the  two  varieties  of  tuberculosis. 

Having  briefly  presented  the  features  of  human  and  avian  tuber- 
culosis, we  may  conclude  that  the  various  bacilli  encountered  in  man, 
mammalia,  and  birds  are  no  more  than  varieties  of  one  and  the  same 
species.  It  is  necessary  to  admit  two  principal  varieties:  one,  desig- 
nated as  human,  attacks  man,  mammalia,  and,  among  the  birds,  the 
psittaci;  the  other,  improperly  called  avian,  is  observed  in  the  gallim~e 
and  sparrows.  Numerous  facts  demonstrate  that  it  is  possible, 
although  difficult,  to  cause  each  of  these  two  bacilli  to  lose  its  so- 
called  specific  properties,  which  means  that  these  properties  are  not 
truly  specific,  since  the  term  species  implies  fixed  virus,  not  suscept- 
ible to  transformation.  Therefore,  in  spite  of  the  differential  char- 
acters of  the  two  great  varieties  of  tuberculosis,  we  conclude  that  the 
disease  is  one. 

1  Larcher.    Melanges  de  pathologie  comparee  et  de  t6ratologie.    Paris,  1878,  p.  153. 


NODULAR   INFECTIONS.  295 

Our  view,  which  is  likewise  thai  of  Drs.  Arloing,  Nocard,  Cour- 
mont,  Dor,  and  others,  leads  to  eonclu  ion    of  practical  importance. 
Since  tuberculosis  may  develop  in  man  through  the  agency  of  the 
avian  bacillus  (Kruse),  tubercular  birds,  and  notably  certain  d 
prepared  with  their  viscera,  should  be  excluded  ae  food. 

The  dangers  of  contamination  are  greater  when  parrots  are  con- 
cerned. In  these  birds  the  bacilli  acquire  extraordinary  virulena 
for  certain  mammalia,  as  was  demonstrated  by  our  inoculations  made 
into  guinea-pigs;  human  t  uberculosis  is  seldom  so  active  upon  these 
small  rodents.  The  bacilli  of  the  diseased  parrol  are  found  in  the 
cutaneous  productions,  saliva,  nasal  mucus,  and  a1  times  in  the 
excrements;  they  may  easily  be  disseminated.  Parrots  contamin- 
ated by  man  thus  become  in  their  I  urn  a  permanent  focus  of  tuber- 
cular infection. 

Pseudotuberculoses. 

The  expression  pseudotuberculosis  is  applied  to  a  series  of  very 

dissimilar  lesions  having  no  other  common  character  than  the  pres- 
ence of  small  tumors,  the  macroscopic  appearance  of  which  resembles 

that  of  tubercle;  in  other  words,  this  group  includes  all  those  i 
in  which  the  granular  lesions  are  not  dependent  upon  Koch's  bacillus. 
It  would  be  logical  to  include  in  the  group  glanders  and  certain 
cases  of  miliary  pyemia.  We  retain  the  expression  because  it  is 
generally  employed.  It  is  advisable,  however,  to  render  its  meaning 
clear  by  an  epithet  specifying  the  kind  of  pseudotuberculosis  con- 
cerned. In  fact,  of  the  latter  there  are  numerous  varieties,  which 
may  be  divided  into  four  groups: 

Pseudotuberculoses  by  inanimate  substances. 

Pseudotuberculoses  by  animal  parasites. 

Mycotic  pseudotuberculoses. 

Bacterial  pseudotuberculoses. 
Pseudotuberculoses  by  Inanimate  Substances.  At  the  time  when 
experimenters  were  endeavoring  to  refute  Villemin's  doctrine  it  was 
asserted  that  any  substance  introduced  into  the  veins  or  peritoneum 
brings  about  the  production  of  tubercles.  These  were  said  to  be 
obtained  by  injecting  pus.  putrefied  muscle,  tissue  fragments,  and 
inorganic  substances.  All  the  results  seemed  to  be  in  harmony,  from 
the  researches  of  Lebert  and  Wyss  down  to  those  of  Cohnheim  and 
Fraenkel,  who  subsequently  changed  their  opinion  and  recognized 
the  specific  nature  of  tubercles. 


296  IXFECTIOUS  DISEASES. 

A  good  many  causes  of  error  had  crept  into  the  experiments. 
.Miliary  abscesses,  infarctions,  granulations  produced  by  inert  sub- 
stances, had  all  been  mistaken  for  tubercular  lesions.  These  granula- 
tions have  been  well  studied  by  H.  Martin,1  who  has  described  three 
principal  varieties:  the  powder  of  cantharides  produces  nodules  com- 
posed of  embryonal  cells;  with  lycopodium  the  lesion  is  characterized 
by  giant  cells  surrounded  by  round  elements;  finally,  Cayenne  pepper 
induces  the  formation  of  true  follicles  composed  of  three  zones  such 
as  are  observed  in  tuberculosis.  Since  histology  was  not  capable  of 
differentiating  these  diverse  granulations,  resort  was  to  be  had  to 
experimentation.  Dr.  Martin  showed  the  pseudotubercles  to  be 
devoid  of  infectious  properties.  Their  inoculation  into  another  animal 
produced  no  lesion,  or  only  a  few  granulations  which  were  no  longer 
inoculable.  On  the  other  hand,  true  tubercle  is  inoculable  in  series, 
and  may  be  transmitted  indefinitely  from  animal  to  animal. 

Analogous  productions  have  been  observed  in  man.  Drs.  Cornil 
and  Toupet  described  a  cutaneous  tubercle  composed  of  follicles,  but 
which  contained  no  bacilli.  Careful  examination  revealed  in  the 
centre  of  the  neoplasm  the  presence  of  small  fragments  of  03^ster-shells 
around  which  the  lesion  had  developed.  Hanan's  observation  is  no 
less  interesting.  At  the  necropsy  of  an  individual  who  died  thirteen 
da}Ts  after  perforation  of  a  round  ulcer,  Hanan  found  numerous 
miliary  granulations  in  the  parietal  peritoneum  and  in  the  adhesions 
which  had  formed  between  the  liver,  diaphragm,  and  duodenum. 
These  granulations  had  the  structure  of  non-caseous  tubercles ;  they 
contained  no  bacilli,  but  hard,  stony  tissue  cells  of  pears. 

Pseudotuberculoses  by  Animal  Parasites.  Pseudotuberculoses 
by  animal  parasites  have  but  exceptionally  been  observed  in  man. 
These  are  small,  yellow,  pale,  or  greenish  tubercles  varying  from  a 
hempseed  to  a  hazel-nut  in  size. 

Among  the  principal  pseudotuberculoses  caused  by  parasites  may 
be  mentioned  that  of  the  cat,  produced  by  the  ollulanus  tricuspis 
(Leuckart) ;  that  of  the  sheep,  called  also  verminous  pneumonia  and 
due  to  the  pseudalius  ovis  pulmonalis  (Koch),  and  that  of  the  calf, 
dependent  upon  the  strongylus  rufescens.  These  pseudotubercu- 
loses are  histologically  characterized  by  simple  agglomerations  of 
embryonal  cells,  and  are,  therefore,  allied  to  glanders  rather  than  to 
tuberculosis.     Such  is  not  the  case  with  the  verminous  tuberculosis 

1  H.  Martin.  Tuberculose  des  sdrenses  et  du  poumon.  Pseudotuberculose  expdri- 
mentale.     Archives  de  physiologie,  1880. 


so  I)  i  I,  !  //  INFECTIONS.  297 

of  the  dog,  produced  by  the  strongylus  vasorum  and  well  studied  by 
Dr.  LaulanieV  This  observer  showed  thai  the  ova  of  strongylu 
arrested  in  the  ramifications  of  Mm-  pulmonary  artery  and  induce 
cellular  proliferation  within  or  around  ili(i  vessel  .  In  the  former 
instance,  at  the  centre  of  the  neoplasm  is  ton  ml  a  giant  cell  containing 
an  ovum  or  an  embryo  surrounded  by  epithelioid  or  embryonal  cells ; 
in  the  latter  case,  when  the  tubercles  are  formed  around  the  v< 
the  artery  undergoes  aneurysmal  dilatation  and  is  surrounded  by  a 
zone  of  gianl  and  epithelioidal  cells. 

Mycotic  Pseudotuberculoses.  Plants  of  a  relatively  higher  or- 
ganism may  cause  the  development  of  granulations  more  or  less 
similar  to  those  of  tuberculosis.  We  shall  first  cite  the  streptoti 
or  oospora,  which  constitute  a  transition  between  bacteria  and  fungi. 
The  interest  attached  to  this  group  is  the  more  considerable,  since, 
as  has  already  been  stated,  the  agent  of  true  tuberculosis,  Koch's 
bacillus,  is  at  the  present  held  to  be  rather  a  streptothrix.  Moreover, 
the.  disease  most  closely  allied  to  tuberculosis,  actinomycosis,  is  due 
to  a  fungus  which  botanists  agree  should  be  classed  with  the  - 
family. 

Among  other  pathogenic  streptothrixse  there  is  one  which  i-  the 
agent  of  the  disease  improperly  called  farcin  of  cattle  {farcin  du 
b(vuf);  this  agent,  discovered  by  Nocard,  who  considered  it  a 
cladothrix,  is  at  present  known  under  the  designations  streptothrix 
oospora,  nocardia  farcinosa. 

The  aspergillus  deserves  a  more  careful  study.  The  aspergillus 
glaucus  and  fumigatus  produce  in  animals  granulations  with  giant 
cells,  at  the  centre  of  which  is  found  the  parasite.  These  facts,  well 
studied  experimentally  by  Kaufmann  and  Lichtheim,  were  com- 
pleted by  the  interesting  investigations  of  Dieulafoy,  Chanter;,  ss 
and  Widal,  Potain,  Gaucher,  Sergent,  and  Renon.  These  authors 
described  a  peculiar  disease  observed  in  men  whose  work  compels 
them  to  handle  grain  or  flour  contaminated  with  the  spores  of  the 
aspergillus  fumigatus.  The  disease  is  ushered  in  as  ordinary  tuber- 
culosis, by  cough,  hemoptysis,  and  a  greenish  expectoration.  The 
sufferer  loses  flesh  and  presents  some  fever  toward  evening.  Auscul- 
tation reveals  bronchitic  rales  and  blowing  respiration,  and  at  times 
signs  of  pleurisy.  In  other  cases  the  beginning  is  announced  by 
bronchitis  and  an  asthma-like  dyspnea  which  grows  worse  at  night. 

1  Laulanio.     Sur  quelques  affections  parasitaires  du  poumon  et  leur  rapport  avec  la 
tuber culose.     Archives  de  physiologie.  iss-j. 


298  INFEl  ■  Tl  <  >  ( rs  DISEASES. 

When  the  disease  is  uncomplicated,  recovery  is  the  rule  after  a 
series  of  ameliorations  and  aggravations  lasting  from  three  to  eight 

years.  Quite  often,  however,  aspergillosis  coexists  with  true  tuber- 
culosis, and  the  latter  is  responsible  for  the  graver  incidents  and  fatal 
termination. 

The  diagnosis  cannot  be  reached  otherwise  than  by  microscopic 
examination  of  the  sputa  and  by  cultures  and  inoculations.  By 
employing  the  fluid  of  Jaulin  cultures  may  be  obtained  within 
forty-eight  hours.  The  intravenous  injection  of  sporulated  culture 
kills  pigeons  in  three  or  four  days,  guinea-pigs  in  four  or  five  days, 
rabbits  in  six  or  eight  days. 

Bacterial  Pseudotuberculoses.  The  great  discovery  of  Koch 
seemed  to  permanently  demonstrate  the  unity  of  tuberculosis.  The 
fact  that  Toussaint  had,  in  1880,  described  a  micrococcus  found  in  a 
tubercular  cow  was  soon  forgotten.  Although  the  author  succeeded 
in  cultivating  the  microbe  and  reproducing  the  disease  in  cats,  the 
results  were  supposed  to  be  due  to  error,  and  no  attention  was  given 
to  them.  It  was,  therefore,  with  a  mingled  feeling  of  surprise  and 
incredulity  that,  in  1883,  the  profession  received  from  Malassez  and 
A  ignal1  the  description  of  a  tuberculosis  due  to  a  parasite  other  than 
Koch's  bacillus.  By  inoculating  a  subcutaneous  tubercle,  taken 
from  a  child  dead  of  meningitis,  these  experimenters  produced  a 
disease  transmissible  in  series  and  apparently  due  to  colonies  of 
zooglea?  which  could  be  seen  at  the  centre  of  the  tubercular  nodules. 
However,  the  fact  that,  in  continuing  their  investigations,  these  gen- 
tlemen noticed  the  gradual  decrease  of  the  zooglese  in  successive  pas- 
sages, brought  doubt  upon  the  individual^  of  the  infection.  Finalty, 
they  were  replaced  by  bacilli  identical  with  Koch's.  Had  an  acci- 
dental contamination  occurred,  as  was  first  believed,  or  a  true  trans- 
formation, as  the  researches  of  Bataillon  and  Terre  tended  to  show? 
According  to  the  latter  hypothesis,  zoogleic  tuberculosis  would  be 
only  a  form  of  true  tuberculosis. 

Zoogleic  tuberculosis  was  found  by  various  authorities.  Castro- 
Sofia  found  the  zooglese  in  an  osseous  abscess  of  the  instep.  Eberth 
encountered  them  in  a  guinea-pig  and  a  rabbit ;  Nocard  in  a  chicken ; 
Manfredi  induced  a  zoogleic  tuberculosis  by  introducing  into  the 
abdominal  cavities  of  guinea-pigs  fragments  of  cotton  through  which 


1  Malassez  and  Vignal.    Tuberculose  zoogl6ique.    Archives  de  physiologie,  1S83.     Sur 
le  mieroorganisme  de  la  tuberculose  zoogleique.     Ibid.,  1884. 


NODULAR  INFECTIONS. 


299 


he  bad  filtered  the  air  of  a  hospital  ward  where  tubercular  patient* 
breathed.    Other  observations  were  reported  by  Grancher,  1/ 
Pfeiffer,  and  ol  hers. 

The  authors  who  firsl  undertook  i  he  si  udy  of  zoogli  ic  tuberculosis 
commonly  contented  themselves  with  microscopic  examinations;  the 
attempts  at  culture  made  by  them  were  insufficient  to  enable  them 
to  specify  the  disease.  Having  the  occasion  to  observes  pseudo- 
tuberculosis develop  spontaneously  in  ;i  guinea-pig,  viz.,  withoul  any 
inoculation,  we  endeavored  to  study  the  disease  more  thoroughly.1 

We  easily  obtained  pure  cultures  of  the  pathogenic  agenl  and 
induced  the  affection  in  various  animal  species.    Though  the  lesion 


Fig.  8. 


Bacillary  pseudotuberculosis.    Hepatic  granulations  with  central  cells  strongly 
stained.       X  150. 


appeared  similar  to  tubercles  when  the  organs  were  examined  with 
the  unassisted  eye.  histological  examination  demonstrated  that  the 
granulations  differed  considerably  from  true  tuberculosis  and  from 
zoogleic  tuberculosis. 

The  lesion  is  of  extreme  simplicity  I  Fig.  8) ;  it  is  a  collection  of 
round  or  epithelioid  cells  with  large  nuclei.  Xo where  is  degeneration 
observable;  the  central  part  is  most  deeply  stained.     On  the  other 

1  Charrin  and  Roger.     Xote  sur  une  pseudotuberculose  bacillaire.     Soc.  de  biologie 
and  Academic  des  science.  1888.     Roger.     Tuberculose  et  pseudotuberculose.     G 
hebdomadaire,  1S90. 


:M,> 


/  XFK ( ■  Tl  0  I S  DISK.  1 N  ES. 


hand,  in  zoogleic  tuberculosis  the  centre  of  the  nodules  appears  like 
a  granular  zone  I  Fig.  9),  and  in  this  zone  the  parasite  accumulates 
in  the  form  of  zooglese.  In  view  of  the  difference  in  their  histological 
features,  we  admitted  that  zoogleic  tuberculosis  and bacillary  pseudo- 
tuberculosis represent  two  distinct  affections.  Such  was  also  the 
(•pinion  of  Dr.  Malassez. 

.More  recently,  however,  zoogleic  tuberculosis  was  again  studied 
by  Drs.  Grancher  and  Ledoux-Lebard,1  Nocard,  and  Masselin,  as  well 
as  Zagari;  these  authors  accurately  indicated  the  characters  of  the 
cultures  and  held  our  disease  to  be  identical  with  that  of  Malassez 
and  Vignal.  We  believe  that  the  histological  study  invalidates  this 
opinion,  and  think  that  these  affections  are  two  different  diseases, 
in  spite  of  their  man}7  points  of  resemblance. 

Fig.  9. 


'':^d&P£/:'^J^.M 


Zoogleic  tuberculosis.     Hepatic  granulations  presenting  three  zoogleic  masses  of 
a  caseous  aspect  and  fragments  of  hepatic  trabecular     X  100. 

Close  to  these  pseudotuberculoses  are:  the  experimental  syphilis 
of  Disse  and  Taguchi,  the  pseudotuberculosis  observed  in  the  guinea- 
pig  by  Morat  and  Doyon,  Bonome,  and  Cipollina;  the  pseudotuber- 
culosis engendered  by  the  inoculation  of  substances  suspected  to  be 
anthrax  (Zagari)  or  the  injection  of  milk  (Parietti) ;  the  pseudotuber- 
culosis spontaneously  appearing  in  the  antelope  (Cornil  and  Toupet), 
and  in  the  hare  (Megnin  and  Mosny). 


1  Grancher  and  Ledoux-Lebard.    Recherches  sur  la  tuberculose  zoogl6ique.    Archives 
de  m£decine  experimentale,  1889  and  1890. 


NODULAR  INFECTIONS.  30] 

Human  Pseudotuberculoses.    The  study  of  bacterial  pseudotuber- 
culoses is  rendered  highly  interesting  by  the  fad  thai  they  occur  in 
man,  as  is  proved  by  the  researchei  of  Mala*  ez  and  Vignal  ' 
Sofia,  Babes,  and  Masselin.    Some  recenl  observations  tend  to 
that  they  are  nol  of  uncommon  occurrence. 

Drs.  Du  C.'i/.'il  and  Vail  lard1  made  a  necropsy  upon  the  cadaver  of 
a  man  who  rapidly  succumbed  to  an  infect  inn  characterized  by  f< 
diarrhea,  and  abdominal  pains.  The  peritoneum  and  pancreae  were 
found  to  be  the  seal  of  ;in  erupl ion  of  caseous  nodules.  These  lesions 
contained  a  large  bacillus,  which  was  cultivated  and  proved  to  I"-  a 
facultative  anaerobic,  liquefying  gelatin  and  imparting  to  the  cultures 
the  odor  of  ammonia.  Its  subcutaneous  inoculation  reproduced  the 
disease  in  the  rabbit,  and  its  intravenous  injection  gave  rise,  accord- 
ing to  the  dose,  to  granulations  or  a  septicemia.  The  guinea-pig 
appeared  refractory. 

A  short  time  after  this  publication,  Dr.  Legrain2  described  a  similar 
bacillus  which  was  associated  with  Koch's  bacillus  in  the  sputa  of  a 
consumptive.  Then  came  the  investigations  of  Bayem  and  Les  a 
who,  in  a  case  of  tuberculosis  of  the  suprarenal  capsules,  found  a 
bacillus  analogous  to  if  not  identical  with  the  one  characterizing  our 
bacillary  pseudotuberculosis.  In  pursuing  the  study  of  this  microbe, 
Lesage  learned  that  it  closety  resembled  the  bacillus  coli  communis. 

We  must  likewise  refer  to  those  cases  of  acute  miliary  tuberculosis 
in  which  Koch's  bacillus  has  not  been  found.  Such  are  the  facts 
reported  by  Kouskow,  Charrin,  and  J.  Courmont.  In  the  two  cases 
published  by  Courmont  the  individuals  were  the  offspring  of  tuber- 
cular parents ;  the  inoculation  of  their  pulmonary  lesions  into  guinea- 
pigs  gave  rise  to  a  rapid,  atypical  tuberculosis. 

Thus  far,  cases  of  pseudotuberculosis  have  been  encountered  in 
man  twelve  times,  ten  times  in  the  rabbit  and  guinea-pig,  twice  in 
cattle  and  sheep,  once  in  the  cow,  the  antelope,  the  hare,  and  the 
chicken.  The  microbes  must  be  widely  distributed  in  the  soil,  as  is 
indicated  by  their  frequent  occurrence  in  small  rodents — guinea-pigs 
and  particularly  in  rabbits — in  which  animals  the  disease,  the  mode 
of  entrance  of  which  is  sufficiently  evidenced  by  intestinal  lesion-, 
at  times  prevails  in  the  form  of  an  epizooty. 

1  Du  Cazal  and  Vaillard.  Sur  une  mala  die  parasitaire  de  l'homme  transmissible  au 
lapin.     Annates  de  l'lnstitut  Pasteur,  1S91. 

:  Legrain.  Sur  une  pseudotuberculose  produite  par  un  baoille  trouve  chez  un  phtisique. 
Bulletin  medical.  1S91. 


302  INFECTIOUS  DISEASES. 

By  collecting  the  observations  thus  far  published  we  reach  the 
following  classification: 

Micrococcic  tuberculosis  of  the  row  (Toussaint,  1880). 
Zo6sl<  ie  tuberculosis  (Malassez  and  Vignal,  1SS3). 
Bacillary  pseudotuberculosis  (Charrin  and  Rojjer.  lssxi. 
Pseudotuberculosis  (probably  zoogkic) 

of  the  guinea-pig  (Zagari,  Bonome,  Cipellina). 

of  the  rabbit  (Dor:  streptobacillary). 

of  the  hare  (Megnin  and  Mosny). 

of  the  antelope  (Connl  and  Toupi  I  i. 
Fetid  bacillary  pseudotuberculosis  (Parietti). 
Pseudotuberculosis  of  the  mouse  (Kutscher,  Galli-Valerio). 
Bacillary  pseudotuberculosis  of  the  sheep  (Preisz  and  Guinard). 
Bacillary  pseudotuberculosis  of  the  hog  (Galli-Val6rio) . 
Human  bacillary  pseudotuberculosis 

of  Du  Cazal  and  Vaillard. 

of  Hayem  and  Lesage. 

of  J.  Courmont. 

of  P.  Courmont. 

Oidiomycosis  or  Endomycosis. 

We  have  repeatedly  stated  that  infectious  diseases  are  character- 
ized by  their  clinical  evolution  and  not  by  the  nature  of  the  causative 
agent.  This  conception  led  us  to  class  with  infections  certain  pro- 
cesses dependent  upon  non-bacterial  parasites — plants  or  even 
protozoa.  The  study  of  the  experimental  disease  which  is  caused 
by  intravenous  inoculation  of  oiclium  albicans  will,  we  believe, 
corroborate  our  argument.  Its  history  represents  for  us  the  type 
of  a  non-bacterial  infection. 

Biology  of  the  Parasite.  It  is  not  necessary  here  to  speak  at 
length  of  the  morphological  and  biological  characters  of  oiclium; 
their  description  will  be  found  in  all  classical  treatises. 

It  is  known  that  the  oiclium  was  found  in  the  productions  of  buccal 
aphtha  by  Langenbec  in  1839,  and  later  studied  by  Berg  in  1841. 
After  researches  by  Gruby  we  must  cite  the  contributions  of  Robin,1 
who  gave  the  parasite  the  name  oidium  albicans,  by  which  it  is  now 
generally  known.  Its  nature,  characters  of  vegetation,  and  patho- 
logical action  were  definitely  fixed  by  the  researches  of  Grawitz, 
Plaut,  Ch.  Audry,  Roux  and  Linossier,  Grasset,  Charrin  and  Os- 
trowsky,  Tessier,  and  Noisette. 

More  recently,  Dr.  Vuillemin  took  up  the  question  from  a  botanical 

1  Robin.  Des  v£ge/taux  qui  croissent  sur  Phomme  et  les  animaux.  These  de  Paris, 
1847.     Histoire  naturelle  des  veg€taux  parasites,  Paris,  1853. 


NODULAR  INFECTIONS. 

standpoint.1  II  was  formerly  believed  thai  the  fungui  of  aphtha 
was  related  to  the  yeasts  and  that  the  filamentoiM  forme  were  of 
but  secondary  importance.  Vuilli  min,  on  the  contrary,  thinks  thai 
Hie  filaments  are  characteristic  and  must  b<  considered  in  cla 
the  parasite;  then,  studying  the  mode  of  reproduction,  he  describe* 
clamydospores  and  endospores.  He  \&]  tn  i  upon  the  presence  of 
a  nucleus  round  both  in  the  globules  and  in  each  filam<  nt<  ment. 

On  the  ground  of  these  importanl  observations  Vuillemin  declares 
the  fungus  of  aphtha  to  be  an  ascomyces  which  si  ion  Id  be  d<  sigi 
as  ( ndonn/ccs  albicans. 

The  expression  oidiomycosis  employed  by  German  authorities 
and  by  (he  author  should  therefore  be  rejected.  When  the  ideas 
of  Vuillemin  are  definitely  accepted  I  shall  he  glad  to  use  the  term 
endomycosis,  as  Miss  .Maria  Daireuva2  writing  under  inspiration  of 
her  master,  Vuillemin,  thinks  1  should.  In  ;i  very  importanl  work, 
Concetti3  classes  this  fungus  with  the  group  of  blastomyces;  accord- 
ing to  this  author,  it  forms  a  transition  between  the  latter  and  the 
hyphomyces  and,  consequently,  the  term  oidimn  albicans  should 
be  preserved. 

If  a  patch  of  buccal  aphtha  be  examined  under  the  microsco]  e 
the  fungus  is  found  to  present  two  different  forms.  At  times  there 
will  be  seen  beautiful  mycelial  filaments;  at  other  times,  rounded 
or  oval  micro-organisms  resembling  yeasts.  These  two  forms  may 
be  associated  or  isolated.  Out  of  thirty-one  examinations  made 
by  us  the  two  forms  were  found  together  nineteen  times.  In  twelve 
cases  there  were  only  the  yeast  forms:  once,  pure  mycelium.  It  is 
possible,  as  is  asserted  b}^  Miss  Daireuva.  that  the  filamental  forms 
are  never  absent.  The  reason  they  are  not  always  detected  is  that 
they  develop  in  the  depth  of  the  cream-like  patch  in  contact  with 
or  inside  the  mucous  membrane. 

The  two  forms  above  indicated  are  encountered  in  artificial 
cultures.  The  oval  form  is  mostly  observed  in  solid  media,  the 
filamentous  in  liquid  media.  These  also  exist  in  solid  media,  but 
are  observed  then  only  at  the  beginning  of  development  (Stocklin) 
or  in  the  deeper  portion  of  the  culture  (Vuillemin.) 


1  Vuillemin.    Los  characteres  specifiques  du  champignon  ilu  muguet.  Comptes  Rendu* 
de  I'Academie  des  Sciences.  October  24.  1S9S. 

2  Maria  Daireuva.    Recherches  sur  le  champignon  du  muguet.    These  de  Pari.-.  18    - 

3  L.  Concetti.     Biologie  et  pathologic  du  muguet.    Archives  de  modecine  des enfant.*. 
August,  1900. 


304  INFEi  'Tl  0  I  rS  DISEASES. 

Characters  of  the  Cultures.  The  fungus  of  aphtha  readily 
develops  in  the  various  nutrient  media  employed  in  bacteriology. 
Agar-agar,  gelatin,   vegetables,   potato,   carrot,  suit    it    well.      In 

liquid  media  the  colonies  soon  fall  to  the  bottom  and  the  fluid 
becomes  clear.  Trine  and  saliva  are  favorable  media,  while  milk 
constitutes  a  had  one.  Of  all  media  the  most  favorable  are  carbo- 
hydrates, especially  glucose  and  saccharose.  Whatever  medium  is 
employed,  the  oidium  gives  rise  to  fermentation  of  carbohydrates, 
resulting  in  the  production  of  alcohol,  aldehyde  and  acetic  acid; 
hence,  the  agreeable  odor  exhaled  by  the  cultures. 

The  isolated  fungi  appear  in  the  form  of  oval  elements,  measuring 
from  5//  to  7//  in  length.  Proliferation  occurs  by  lateral  or  termi- 
nal budding.  If  a  bouillon  or  serum  culture  be  examined,  the 
filamentous  forms  are  seen  measuring  3//  to  4//  in  breadth  and  15/* 
to  20//  in  length,  which,  in  some  instances,  may  exceed  400//  or 
even  500//. 

It  is,  therefore,  easy  to  prove  the  diplomorphism  of  oidium  by 
employing  solid  or  fluid  medium.  It  may  be  assumed  that  the 
filamentous  form  which  predominates  in  fluid  media  is  due  to  the 
lack  of  oxygen;  unable  to  vegetate  upon  the  surface  of  the  fluid, 
where  no  film  is  ever  formed,  the  fungus  falls  to  the  bottom,  and 
then  sends  out  prolongations  toward  the  aerated  surface.  When 
it  is  cultivated  in  a  very  shallow  liquid  medium  the  filaments  are 
seen  to  become  shorter. 

Other  conditions  also  influence  filamentous  growth.  The  yeast 
form  predominates  when  the  plant  is  placed  under  eugenesic  con- 
ditions; when  the  media  are  less  favorable  the  filamentous  forms 
prevail. 

Although  the  descriptions  given  by  authors  are  mainly  in  harmony, 
they  differ  in  many  details.  These  differences  in  opinion  are,  in 
great  measure,  clue  probably  to  the  fact  that  aphtha  comprises 
several  varieties. 

Role  of  the  Oidium  in  Human  Pathology.  The  fungus  of  aphtha  is 
pathogenic  for  man  and  certain  animals.  In  the  colt,  calf,  sheep, 
and  hen  it  produces  a  white  stomatitis  which  often  spreads  to  the 
esophagus,  presenting  the  same  characters  as  in  man. 

Oidian  stomatitis,  also  called  creamy  stomatitis  (stomatite 
cremeuse),  aphtha,  and  thrush,  is  commonly  observed  in  weakened 
or  cachectic  individuals,  in  the  course  of  diseases  which  profoundly 
debilitate  the  system,  grave  typhoid  fever,  urinary  and  tubercular 


NODULAR  INFECTIONS. 

infections,  cancer,  diabetes,  etc.  As  Gubler  has  shown,  it*  develop- 
ment is  favored  by  the  acidity  of  the  mucous  membrane.  The 
acidity  is  due  to  the  excessive  multiplication  of  microbes  and  to 
fermentations  which  they  produce  in  the  food,  particularly  in  milk. 
Thus  is  produced  a  catarrhal  stomatitis  which  weaken*  there  i  tance. 
The  agents  of  aphtha  being  spread  in  the  atmosphere  (Lebrun, 
Etoux,  Valtat),  easily  develop  in  the  altered  buccal  mucous  mem- 
brane. In  oilier  instances  the  parasite  i  transmitted  directly 
through  the  nursing  bottle  or  the  breast  of  the  nurse  who  suckles 
several  children.  Finally,  it  maycomefrom  the  milk,  which  is  often 
polluted  with  oidium  lach'x,  ;i  plan!  closely  related  to  the  aphtha 
parasite. 

It  is  true,  however,  thai  aphtha  does  sometimes  develop  in  healthy 
individuals,  in  children  by  no  means  athrepsic,  in  non-cachectic 
aged  persons,  and  at  the  beginning  of  certain  infections,  notably 
typhoid  fever.  It  is  also  encountered  in  the  mosl  varied  forms 
of  angina.  In  a  total  of  31  cases  of  diphtheritic  angina  thewriter 
found  it  twice;  of  46  cases  of  non-diphtheritic  angina  1  showed 
it  combined  with  the  streptococcus;  of  116  cases  of  scarlatinal 
angina  4  presented  it. 

Dr.  de  Stocklin's  statistics  show  the  presence  of  the  oidium  in 
5.75  per  cent,  of  diphtheritic  cases,  and  10.5  per  cent,  of  non-diph- 
theritic angina. 

The  role  of  the  oidium  albicans  in  these  various  anginas  appears 
to  be  of  slight  importance.  Such  is  not  the  fact,  however,  when  we 
consider  certain  observations  of  oidian  angina  progressing  as  acute 
sore  throat.  Teissier  reported  a  case  of  this  sort.1  A  woman, 
twenty-three  years  of  age,  was  abruptly  seized  with  chills,  malaise, 
headache  and  fever.  The  following  day  she  suffered  from  intense 
dysphagia.  Examination  of  the  throat  showed  two  small  white 
delicate  membranous  patches  upon  the  palate  which  adhered  slightly 
to  the  mucous  membrane.  The  exclusive  presence  of  the  oidium 
albicans  was  observed  under  the  microscope.  In  this  instance 
well  as  in  that  reported  by  Guimbretiere,2  oidian  mycosis  started 
and  ran  its  course  as  an  infection;  chills,  malaise,  and  fever  were 
the  clinical  features.     No  one  would  hesitate  to  consider  these  mani- 

1  Teissier.  Angine  pseudomembraneuse  produite  par  le  champignon  du  rauguet. 
Arch,  de  nn'-d.  exp.,  1S95. 

-'  Guimbretiere.  Essai  sur  I'angine  pseudomembraneuse  due  au  rnuguet.  These  de 
Toulouse.  1896. 

20 


306  I. \FECTIO US  DISEASES. 

festations  as  infections,  if,  instead  of  a  fungus,  a  bacterium  was 
detected! 

I  have  observed  a  certain  number  of  similar  eases.  Every  year 
a  few  patients  'with  acute  oidian  angina  are  admitted  to  our  wards. 
In  1899  we  had  three  such  cases.  It  will  suffice  to  mention  one  of 
them,  a  woman,  twenty-three  years  old,  who  had  chills,  violent 
headache,  and  dysphagia,  A  physician  called  in  on  the  following 
day  diagnosed  diphtheria  and  advised  her  removal  to  the  hospital. 
Here  we  found  her  throat  red,  the  tonsils  greatly  enlarged,  and 
white  creamy  patches  the  size  of  a  pea  occupied  the  soft  palate, 
right  pillar,  right  tonsil  and  uvula.  Our  immediate  diagnosis  was 
aphtha,  and  microscopic  examination  demonstrated  the  presence 
of  both  mycelium  and  fungus.  It  required  eight  days'  treatment 
to  bring  about  recovery. 

The  oidium  ma}'  be  encountered  in  other  mucous  membranes 
exposed  to  the  air.  It  may  invade  the  respiratory  apparatus, 
pharynx,  esophagus,  or  the  intestinal  canal.  In  the  stomach  it  may 
penetrate  into  the  glandular  cul-de-sacs  and  ulcerate  them.  Valleix 
and  Seux  noted  its  presence  in  the  small  intestine  and  cecum.  It 
has  been  observed  in  the  anus,  vulva  and,  according  to  Senator  and 
v.  Fritsch,  even  in  the  mucous  membrane  of  the  bladder. 

Whatever  may  be  its  seat,  the  lesion  created  is  of  a  benign  char- 
acter and  commonly  of  slight  tenacity.  This  fungus  does  not 
represent,  however,  a  simple  epiphyte.  Virchow,  Wagner,  Parrot, 
and  Letulle  have  seen  it  penetrate  quite  deep  into  the  mucous  mem- 
branes. Examining  the  cadavers  of  thirty-eight  children  who  had 
succumbed  to  aphtha,  Heller  found  in  two  cases  the  presence  of  the 
parasites  in  the  bloodvessels;  the  latter  were  the  seat  of  thrombosis 
in  six  cases.  It  is,  therefore,  conceivable  that  the  fungus  may  be 
carried  by  the  lymph  and  blood  currents  to  the  various  parts  of  the 
system.  In  fact,  it  has  been  observed  in  otitis  media  (Valentin), 
abscess  of  the  gums  (H.  Grasset),  submaxillary  abscess  (Charrin), 
and  suppurating  parotiditis  (Guido).  At  the  necropsy  of  a  man 
who  died  with  right  hemiplegia,  Zenker1  found  the  left  cerebral 
hemisphere  full  of  small,  round,  granular  abscesses,  containing  the 
parasite.  The  starting-point  was  attributed  to  the  thick  membranes 
of  aphtha  occupying  the  throat.  This  is  the  first  observation  of  the 
kind. 

1  Zenker.  Soor  in  Gehirnabscessen.  Berichte  der  Gesellschaft  f.  Natur  unci  Heil- 
kur.de,  1861. 


NODULAR  INFECTIONS.  307 

In  a  child  who  died  from  9  buccal  aphtha  twelve  days  after  birth 
Ribbert1  round  both  cerebral  hemi  phere  tudded  with  miliary 
abscesses,  containing  oidian  filaments.  G.  Guidi2  has  likewise  found 
the  oidium  in  the  pus  of  cerebral  abscesses  in  a  girl  three  years  old. 
Finally,  Dr.  Monier8  published  the  observation  of  a  cerebral  oidian 
abscess  expressing  itself,  during  life,  by  hemiplegia  with  Jacksonian 
epilepsy. 

Thf  respiratory  apparatus  may  also  be  invaded  in  certain  cs 

The  oidium  lias  been  found  in  the  pneumonic  torn-  in  :i  four-yar-old 

child,  in  the  lung  of  a  little  girl  suffering  from  fetid  bronchitis,  and 
in  a  pulmonary  lesion  simulating  a  hydatid  cysl  of  the  liver.    Guidi 

observed  the  parasite  in  a  pulmonary  absceS£  occurring  in  a  child 
three  months  old,  which  perforated  a  pulmonary  artery,  and  thus 
caused  sudden  death  by  hemorrhage. 

In  some  instances  the  nature  of  the  disease  has  been  recognized 
during  life.  In  an  observation  of  Preyhan,  the  patient4  suffered 
from  pulmonary  disease,  with  hemorrhagic  pleurisy;  her  expectora- 
tion was  sanguinolent  and  exhaled  the  odor  of  fresh  yeast,  and 
contained  clots  formed  of  the  fungi  of  aphtha. 

Oidian  lesions  have  been  observed  in  the  various  segments  of  the 
digestive  tract,  notably  in  the  stomach  and  intestine.  In  an  observa- 
tion of  Schmorl5  the  parasite  invaded  the  kidneys  and  there  pro- 
duced miliary  abscesses  occupying  the  surface  of  the  organs. 

These  observations  are  very  interesting,  since  they  demonstrate 
that  oidiomycosis  such  as  is  experimentally  produced  in  animals 
is  a  possible  event  in  human  pathology,  and  probably  of  more 
frequent  occurrence  than  the  cases  reported  seem  to  indicate. 

Experimental  Oidian  Mycoses.  Klemperer6  is  to  be  credited 
with  having  demonstrated  that  intravenous  injection  of  a  culture 
of  the  oidium  albicans  induces  a  fatal  disease,  characterized  by 
numerous  granulations  in  the  kidneys. 

1  Ribbert.  Weitere  Untersuchungen  liber  das  Sehiksal  pathogener  Pilze  ini  organis- 
mus.     Deutsche  med.  Wochenschrift,  1SS5. 

2  Guidi.  Ueber  Soor,  seine  Mykologie  und  Metastasenbildung.  Wiener  med.  Blatt., 
1S95. 

3  Monier.  Considerations  sur  les  mycoses  ceri'brales  et  plus  particulierement  sur  la 
generalisation  dumuguet.  Gaz.  mod.  de  Nantes,  1S97.  Pineau.  Le  muguet  infectieux. 
These  de  Paris,  1S97. 

4  Preyhan.     Pneumonomycosis.     Berliner  klin.  Wochenschrift.  1891. 

5  Schmorl.  Ein  fall  von  Soormetastase  in  der  Xiere.  Centralblatt  f.  Bakteriologie, 
1891,  Bd.  ix. 

6  Klemperer.     Ueber  die  Xatur  des  Soorpilzes.     Ccntralb.  f.  klin.  Medicin.  l^v". 


308  IXFECTIO  US  DISEASES. 

Experiments  of  Roux  and  Linossier  showed  the  possibility  of 
nervous  symptoms  in  the  inoculated  animals.  My  own  researches 
confirm  the  descriptions  of  these  authors  and  demonstrate  the 
frequency  and  variability  of  the  nervous  phenomena. 

The  more  numerous  experiments  of  Grasset1  added  some  new 
facts.  These  investigations  show  that  intravenous  injection  pro- 
duces foci  not  only  in  the  kidneys,  but  at  times  also  in  the  peri- 
toneum, liver,  intestine,  heart,  and  spleen.  The  suprarenal  capsules 
are  the  seat  of  lesions  appreciable  only  under  the  microscope. 

The  first  researches  which  I  published  on  this  subject2  com- 
pleted our  knowledge  of  the  localizations  of  the  oiclium,  the 
histological  characters  of  the  lesions,  exaltation  of  virulence,  and 
particularly  the  modifications  presented  by  the  serum  of  vaccinated 
animals. 

After  inoculation  the  animals  remain  healthy  for  a  day  of  two; 
then  they  begin  to  emaciate.  Death  may  occur  suddenly.  It  is 
often  preceded  by  paralytic  manifestations  which,  with  certain 
cultures,  are  seldom  wanting.  The  morbid  phenomena  grow  worse, 
and  the  animal  succumbs  in  a  state  of  general  exhaustion  after 
suffering,  in  some  cases,  from  convulsions.  The  necropsy  reveals 
granulations  disseminated  in  various  parts  of  the  organism. 

Histological  Study  of  the  Oidian  Tubercle.  The  histological  ex- 
amination must  be  directed  to  the  kidneys  invaded  with  nodules.3 
In  preparations  stained  with  alum-carmine,  and  picrocarmine,  the 
granulations  appear,  under  slight  magnification,  in  the  form  of 
small  masses,  which  are  distinguished  from  the  surrounding  tissue 
by  then  red  color;  their  limits  are  not  absolutely  clear  and  sharp. 
Rows  of  cells  extend  from  the  granulations  and  form  prolongations 
which  enter  the  tubules  of  the  kidney.  When  more  highly  magnified 
the  nodules  are  seen  to  be  composed  of  collections  of  embryonal 
cells,  the  yellowish  portions  corresponding  to  degenerated  elements 
fused  into  a  homogeneous  mass  (Fig.  10). 

Vaccination  Against  the  Oidium.  Noisette  has  shown  that  the 
fungi  of  aphtha  degenerate  when  cultivated  in  the  serum  of  animals 
previously  infected  with  the  mycotic  fungus,  and  a  short  time  after- 

1  Grasset.  Etude  d'un  champignon  pyogene  parasite  de  l'homme.  Arch,  de  med. 
exp.,  Sept.,  1893.     Etude  sur  le  muguet.    These  de  Paris,  1894. 

2  Roger.  Modifications  du  serum  chez  les  animaux  vaccines  contre  l'oidium  albicans. 
Soc.  de  biologie,  July  4,  1896. 

3  Roger  and  Josue.  Des  alterations  du  rein  dans  l'oi'diom3rcose  experimehtale. 
Societe  anatomique,  January  2,  1897. 


NODULAR  INFECTIONS. 


309 


ward  they  cease  to  multiply.  This  reaction  was  taken  advantage 
of  by  the  author  in  differentiating  the  diverse  varieties  of  oidium 
separated  by  him. 

I'm;.    10. 


The  upper  figure  represents  a  normal  kidney :  the  middle  one  a  highly  hypertrophied 
kidney  whose  surface  is  covered  with  oidium  granulations;  the  lower  figure  represents 
a  transverse  section  of  the  diseased  kidney  (natural  size). 


The  serum  of  vaccinated  animals  acts  more  energetically  upon 
the  plant  than  that  of  infected  ones.     In  fact.  I  have  learned  that 


310  INFECTIOUS  DISEASES. 

it  is  possible  to  confer  quite  a  remarkable  degree  of  immunity  upon 
the  rabbit.  To  succeed  in  this  experiment  it  is  necessary  to  begin 
with  a  weak  culture,  of  which  a  very  small  dose  is  injected  into  the 
veins.  Tin"  doses  must  be  slowly  and  progressively  increased  until 
the  animal  is  able  to  endure  twice  or  even  three  times  the  fatal 
amount. 

The  Agglutinating  Power  of  the  Serum.  Having  succeeded  in 
conferring  a  notable  degree  of  immunity  upon  the  animals,  the 
writer  was  naturally  led  to  investigate  whether  the  serum  of  the 
animals  thus  treated  manifested  modifications  similar  to  those 
observed  in  animals  which  had  received  various  bacteria.  First 
studying  the  serum  of  animals  submitted  to  subcutaneous  and 
intraperitoneal  inoculations,  he  noticed  that  aphtha  develops  in 
this  medium  as  well  as  in  the  normal  serum.  This  result  need  not 
be  wondered  at,  since,  under  these  conditions,  there  has  been  no 
increase  in  resistance.  If,  however,  the  serum  of  rabbits  vaccinated 
by  intravenous  inoculations  be  studied,  other  results  are  obtained. 

Let  us  take  a  culture  grown  in  normal  serum  and  inoculate  a 
trace  of  it  into  twro  tubes,  one  containing  normal  serum,  the  other 
serum  of  the  vaccinated  animal.  At  the  end  of  twenty-four  hours 
development  is  very  luxuriant  in  the  normal  serum.  In  the  other 
serum  a  few  flocculi  occupying  the  bottom  of  the  tube  may  at  times 
be  seen ;  at  other  times  no  development  is  apparent,  the  fluid  remains 
perfectly  clear.  At  the  bottom  of  the  tube,  however,  there  is  found 
an  accumulation  of  small  granules  which  manifest  a  strong  tendency 
to  agglutinate  so  as  to  sometimes  form  a  single  mass.  When  the 
fluid  is  shaken  the  granules  are  dispersed,  but  are  not  numerous; 
the  culture  is  a  poor  one.  Increased  development  is  observed  on 
the  following  days,  but  the  culture  remains  long  or  always  inferior 
to  that  of  the  control. 

The  vegetating  power  of  the  oidium  becomes  so  weakened  in  the 
serum  of  the  vaccinated  animal  that  if,  at  the  end  of  four  or  five 
days,  another  tube  containing  the  same  kind  of  serum  be  inoculated 
with  this  culture,  the  fluid  remains  sterile. 

A  microscopic  examination  will  suffice  to  show  why  the  cultures 
present  such  different  aspects. 

At  the  end  of  twenty-four  hours  the  normal  serum  contains 
(Fig.  11)  filaments  associated  with  yeast  forms;  the  latter,  at  times 
provided  with  a  terminal  or  lateral  bud,  are  formed  of  a  mass  of 
protoplasm  deeply  stained  with  methylene  blue  and  limited  by 


NODULAR  INFECTIONS. 


31  1 


:i  very  thin  and  colorless  cuticle.    These  fungi  are  free,   olil 
or  united  into  groups  of  twos  and  three  .  Even  when  thus  adher- 
ing it  is  readily  seen  thai  each  of  them  hac  ite  proper  individuality; 
their  cuticles  are  clearly  distinct;  there  i-  only  juxtaposition,  bul 
no  fusion  with  neighboring  elements. 

The  filamentous  forms  differ  from  the  preceding  by  the  more 
pronounced  development  of  their  cuticles,  the  small  amounl  of  their 


i;ii,  ii 


Appearance  of  a  culture  of  oidium  albicans  in  a  normal  serum.  Beautiful  fila- 
ments are  seen  alongside  of  .yeast  forms,  at  times  provided  with  a  terminal  or  lateral 
bud.  The  non-homogeneous  protoplasm  presents  dark  and  light  parts;  it  is  limited 
bv  a  thin  and  colorless  cuticle. 


protoplasm,  and  weaker  affinity  for  the  aniline  dyes.  The  filaments 
are  undivided,  ramified,  or  provided  with  lateral  buds  having  the 
form  of  yeasts. 

When  the  culture  developed  in  the  serum  of  the  vaccinated  animal 
is  examined  the  appearances  are  found  to  be  quite  different. 

Let  us  first  consider  a  solitary  fungus :  The  protoplasm  is  colored 
as  in  the  normal  state;  it  has  the  same  appearance  and  dimensions. 


312 


IXFECTIO  US  DISEASES. 


It  is  surrounded  by  a  colorless,  hyaline,  at  times  a  slightly  striated 
mass,  with  sinuous,  illy-defined  borders,  the  length  of  which  is  five 
or  six  times  that  of  the  normal  cuticle.  The  elements  are  seldom 
isolated:  they  form  couplets,  groups  of  three,  and  often  groups  of 
voluminous  sizes,  made  up  of  from  ten  to  thirty  elements.  It  is 
easy  to  demonstrate  that  the  condition  here  is  not  one  of  simple 
juxtaposition,  but  one  of  fusion  of  the  cuticles  and  formation  of  a 
true  zooglea.  The  filaments  are  here  and  there  intimately  united 
to  the  fungi,  which  are  either  solitary  or  agglutinated.     In  other 


Fig.  12. 


Appearance  of  a  culture  of  oidrum  albicans  in  the  serum  of  the  vaccinated  animal. 
The  elements  are  united  in  voluminous  agglomerations  and  surrounded  by  a  colorless 
hyaline  mass.  The  filaments  are  likewise  composed  of  a  protoplasmic  mass  surrounded 
bv  a  very  thick  cuticle. 


instances  one  extremity  of  a  filament  is  lost  in  the  midst  of  a  collec- 
tion of  fungi  to  which  it  seems  to  have  fused. 

Conclusions  Concerning  the  Nature  of  Oidiomycosis.  Oidio- 
mycosis does  not  differ  from  bacterial  infections  any  more  than  the 
latter  do  from  each  other.  In  fact,  it  is  evidently  possible  to  express 
in  one  general  formula  the  mode  of  action  of  the  various  bacteria. 
When,  however,  we  come  to  considerations  of  general  pathology, 
we  reach  conclusions  which,  in  the  majority  of  instances,  are  appli- 
cable only  to  certain  groups  of  microbes,  but  not  to  all.  Oidiomycosis 
is,  therefore,  not  to  be  compared  to  a  schematic  bacterial  infection; 


NODULAR  INFECTIONS.  313 

the  question  is  whether  ii  resembles  some  well-determined  infec 
disease.     By  reason  of  the  lesions  ii  produces  in  animals,  the  oidium 
closely  resembles  the  pyogenic  microbes,  notably  the  3taphylococ 
Indeed,  in  both  cases  subcutaneou    inoculation  La  followed  by  the 
formation  of  an  abscess.     When  injected  into  the  vein-  the  staphy- 
lococcus, like  the  fungus  of  aphtha,  gives  rise  to  miliary  ab  <■• 
The  analogy  is  continued  even  in  the  localization,  since  the  staphylo- 
coccic abscesses  are  often  confined  to  the  kidneys;  occasionally  the 
cocci  invade  other  organs,  notably  the  myocardium,  liver,  lungs, 
and  brain.     The  oidium  is  equally  capable  of   affecting  the  same 
organs  in  the  same  manner. 

Moreover,  vaccination  againsl  oidiomycosis  is  as  practicabli 
in  bacterial  infections.  We  have  further  3een  that,  in  the  -'rum 
of  animals  vaccinated  against  oidiomycosis,  modifications  similar 
to  those  observed  in  animals  vaccinated  againsl  bacteria  are  pro- 
duced. In  both  cases  the  serum  becomes  bactericidal;  ii  inhibits 
and  weakens  the  development  of  the  pathogenic  agent. 

The  idea  of  infection  is  not  established  on  etiological  or  patho- 
genical  bases,  but  on  clinical  data,  to  wit,  on  the  reactionary  modes 
of  the  affected  system.  The  facts  above  stated  demonstrate  thai 
the  organism  acts  toward  the  oidium  as  it  does  toward  bacteria. 
Oidiomycosis,  then,  is  rightly  classed  with  infectious  diseas  3. 

Pathogenic  Role  of  Yeasts. 

The  study  of  oidium  is  rendered  particularly  interesting  by  the 
fact  that  this  plant  represents  the  best  known  member  of  an  im- 
portant group  of  pathogenic  agents.  In  reality,  a  great  number 
of  yeasts  give  rise  to  similar  lesions.  Thus.  Miss  L.  Rabinowitsch1 
out  of  fifty  species  of  yeasts  taken  in  Koch's  laboratory  found 
seven  pathogenic  ones.  Noisette,  employing  a  certain  yeast  that 
is  currently  on  the  market,  showed  that  its  inoculation  produced  a 
mycosis  similar  to  that  caused  by  the  oidium  albicans.  San  Felice2 
found  in  the  juice  of  fermented  fruits  a  pathogenic  yeast,  the  sac- 
charomyccs  neo  for  mans . 

We  may  also  cite  the  saccharomyccs  lithogens  of  San  Felice,  the 
<S.   niger  of  Maffucci  and  Sirleo,  the  S.  sepdcus  of  Gaetano,  etc. 

1  Lydia  Rabinowitsch.  Untersuchungen  uber  pathogen  Hefearten.  Zeitschrift  f. 
Hygiene,  1S95,  Bd.  xxi. 

':  San  Felice.  Ueber  eine  fur  Thiere  pathogene  Spros>pilzart.  Oentralblatt  f.  Bak- 
teriologie.  1893.  Bd.  xvii. 


314  TNFEi  ■  TIO  I 'S  DISEASES. 

Bere,  ;lu'ii.  are  widely  distributed  plants,  some  of  them  daily  em- 
ployed in  the  industries,  which  are  capable  of  engendering  diseases. 

It  may  be  objected  that  these  are  merely  experimental  results, 
and  thai,  in  order  to  produce  them,  such  procedures  have  been 
resorted  to  a-  are  never  realized  in  the  natural  course  of  events.  It 
is  well  to  know,  however,  that  yeasts  are  frequently  found  in  the 
organism.  Their  presence  has  been  noted  in  cutaneous  ulcers 
I  Babes),  in  suppurated  dental  pulps  (Miller),  in  uterine  and  vaginal 
discharges  (Colpe),  in  hypertrophied  tonsils  (de  Simoni),  in  the  brains 
of  hydrophobic  men  and  animals  (Memmo),  and  cultures  of  these 
parasites  have  at  times  produced  fatal  disturbances  in  animals. 

Recent  contributions  tend  notably  to  increase  the  role  of  yeasts 
in  pathogenesis.  An  interesting  observation  of  chronic  pyemia  was 
reported  by  Busse.1  The  symptoms  were  due  to  a  saccharomyces 
the  cultures  of  which  induced  in  animals  disturbances  similar  to 
those  observed  in  man.  There  appeared  also  a  series  of  contributions 
demonstrating  that  in  man,  as  well  as  in  certain  animals,  blasto- 
mycetes  are  frequently  encountered  in  various  neoplasms  (San  Felice, 
Roncali,  Corselli  e  Prisco,  Ajevoli,  Secchi,  Wlaeff,  etc.).  It  will 
suffice  to  mention  one  among  the  numerous  observations,  that  of 
Curtis.2  It  was  a  case  of  a  myxosarcoma  of  the  thigh,  comprising 
yeast  in  a  state  of  purity  which  was  successfully  inoculated  into 
the  connective  tissue  of  a  rabbit.  This  does  not  mean  that  yeasts 
represent  the  exclusive  agents  of  tumors,  but  they  really  seem  to 
give  rise  to  some  of  them.  This  is  sufficient  inducement  to  draw 
more  attention  to  their  study. 

We  are  thus  in  the  presence  of  a  new  chapter,  in  its  formative 
stage,  in  the  history  of  infectious  diseases.  Blastomycetes  claim  a 
place  alongside  bacteria  and  streptothrix.  Oidiomycosis  may  now 
be  considered  as  the  type  of  mycotic  infections. 

Actinomycosis. 

Biological  Characters  of  Actinomyces.  Actinomycosis  is  a  disease 
due  to  the  presence  of  a  special  plant  belonging  to  the  class  of  strepto- 
thrix or  oospora,  and  occurring  in  the  form  of  radiate  collections 
visible  to  the  naked  eye.     They  are  small,  yellow,  opaque  grains  of 

1  Busse.  Ueber  parasitare  Zelleinschlusse  und  ihre  Ztichtung.  Centralb.  f.  Bakte- 
riologie,  1895,  Bd.  xvi.    Ueber  saccharomyces  hominis.    Virchow's  Archiv,  1895,  Bd.  cxl. 

2  Curtis.  Contribution  a  1 'etude  de  la  saccharomycose  humaine.  Annales  de  l'Institut 
Pasteur,  1896. 


nodu LA  B  INFECTIONS. 


316 


variable  size.  Commonly  of  ;i  golden  yellow  color,  when  young 
I, hey  are  whitish  and  translucent;  in  other  instance  their  color  i- 
dark  green  or  sepia. 

The  grain  may  easily  be  crushed.  It  is  formed  of  small  balls 
measuring  from  0.3/*  to  0.5/*  in  breadth  and  0.18ft  to  0.35/i  in 
length,  and  when  slightly  magnified  it  appears  in  mulberry  form. 

Each  granulation  is  composed  of  a  central  ma  I  ig.  L3j,  whence 
numerous  prolongations  radiate,  mosl  of  which  end  ina  club-shaped 
enlargement.  These  enlargements  were  once  considered  to  be 
bearing  organs,  bul  they  simply  represent  mycelial  involution  swell- 
ings. Their  weak  vitality  explains  their  frequenl  infiltration  with 
calcareous  salts. 

Fir;.   13. 


Granulation  of  actinomycosis.      X  600. 

The  actinomyces  resist  the  action  of  acids,  alkali,  chloroform,  ami 
ether;  hot  alkalies  render  them  pale  and  disfigure  them :  water,  even 
salt  water,  swells  and  deforms  them. 

Cultivation  of  Actinomyces.  Actinomyces  has  quite  often  been 
successfully  cultivated  in  the  artificial  nutrient  media  employed  in 
bacteriology.  Solidified  serum  was  employed  by  Irsael.1  Small 
nodules  composed  of  grains  similar  to  those  observed  in  the  actino- 
mycotic lesions  of  man  and  animals  made  their  appearance  in  the 
medium  on  the  fourth  day.     Development  is  very  active  on  glycerin- 


1  Israel.  Ueber  die  Cultivirbarkeit  d.  Actinomyces.  Virchcw's  Arch..  1SS4.  Bd.  xcv. 


3 1 6  INFECTIO  US  DISEA  SES. 

ated  agar-agar;  according  to  Kischensky,1  colonics  containing  rods 
similar  to  tubercle  bacillus  appear  as  early  as  the  second  day;  then 
there  appears  a1  each  extremity  a  swelling  which  stains  intensely. 
Toward  the  sixth  or  seventh  day  the  rods  become  elongated  into 
filaments  which,  after  two  or  three  weeks,  bear  at  their  extremities 
involutive  forms  which  can  no  longer  be  stained. 

Actinomyces  may  also  be  cultivated  in  liquid  media,  such  as 
serum,  milk,  and  bouillon.  Cultures  succeed  also  upon  potatoes  and 
in  eggs. 

The  spores  never  occur  in  living  organisms.  They  are  encoun- 
tered only  in  artificial  cultures,  to  which  they  impart  a  notable 
resisting  power. 

Fig.  14. 


Culture  of  actinomyces  in  bouillon,  seven  months  old,  after  twenty-four  hours'  incu- 
bation. Numerous  filaments  with  club-shaped  extremities  (to),  hyaline  bulbs  (g), 
representing  clubs  in  process  of  degeneration,  and  a  few  spore-bearing  filaments 
(s).      (Berard  and  Nicolas.) 

Actinomyces  has  been  variously  designated  and  classed  by  different 
authorities.  The  point  conclusively  established  is  that  it  is  not  a 
bacterium,  but  a  fungus,  to  be  placed  permanently  beside  the 
streptothrix. 

Inoculation  of  Actinomyces.  Johne  was  the  first  successfully  to 
inoculate  actinontyces,  by  operating  upon  a  heifer  and  two  calves. 
It  has  since  been  possible  to  produce  the  disease  in  the  rabbit  and 
guinea-pig,  but  not  invariably.     The  best  results  are  obtained  by 

1  Kischensky.  Ueber  Actinomj-cesreinculturon.  Arch.  f.  exp.  Path,  und  Pharmakol, 
18S9. 


NODULAR  INFECTIONS.  .",17 

the  employment  of  anaerobic  culturei  or  tho  e  made  in  i  ■  ■  Lieb- 
man1  thinks  the  failures  are  due  to  the  supposed  facl  that,  unlike 
the  great  majority  of  virulenl  agenl  .  actinomyces  is  attenuated  in 
passing  through  the  bodies  of  man  and  animal  ;  al  the  same  time 
its  vegetability  diminishes  in  notable  proportions.  If  would  be 
possible  for  the  parasite  to  recover  its  powers  of  vegetation  and 
virulence  by  cultivation  in  a  plant.  Various  experimenters,  how- 
ever, unsuccessfully  repeated  the  experiments  of  Liebman. 

Etiology.  While  very  frequenl  among  certain  animals,  especially 
the  l)ovidav,  actinomycosis  is  qoI  rare  in  man.  In  Bergmann's 
clinics  in  Berlin  L20  cases  were  collected  in  six  years.  Num< 
observations  have  been  reported  in  France,  Switzerland,  Bolland, 
and  England.  In  America  the  firsl  case  was  observed  in  L888  by 
Bulhoes  and  Magalhaes.  Since  that  time  a  greal  oumber  of  - 
have  been  observed  in  the  New  World;  actinomycosis  seems  to 
be  of  frequent  occurrence  there,  and  renders  suspicious  the  meal 
imported  to  Europe. 

Actinomycosis  may  be  observed  in  horses,  sheep,  and  hogs,  the 
infection  originating  from  plants  upon  which  these  animals  are  fed. 
Men  are  also  often  affected  in  the  same  manner,  in  handling  plants 
or  accidentally  swallowing  ears  of  barley,  and  in  many  other  ways 
which  often  remain  unrecognized.  Alongside  the  cereals  we  musl 
place  the  young  shoots  of  thorny  shrubs  and  the  bark  of  v 
altered  by  moisture  and  mouldiness. 

It  is  well  to  mention  that  the  parasite  has  been  found  in  milk 
(Bollinger)  and  eggs  (Artant),  hence  the  possibility  of  contamination 
by  food. 

Evolution  of  Actinomycosis.  The  anatomical  and  clinical  evo- 
lution of  actinomycosis  is  different  in  man  and  in  animals.  In 
man  suppurating  foci  are  encountered:  in  animals  hard  tumors, 
resembling  sarcoma.  It  was  once  believed  that  these  differences 
depended  upon  differences  in  the  parasites.  The  study  of  etiology, 
however,  and  especially  the  experiments  of  Irsael.  Bostroem,  and 
Rotter,  who  transmitted  the  disease  from  man  to  animals,  demon- 
strated the  unity  of  the  infection.  The  peculiar  characters  of  the 
malady  in  man  are  due  to  the  fact  that  the  parasite  is  associated 
with  common  pyogenic  microbes  which  add  their  action  to  tl.; 
the  actinomyces.     In  certain  observations  in  which   actinomyces 

1  Liebman.     L'actmomice  dell'  nomo.     Archiv  per  le  sc.  med.,  1890. 


:  1 1  8  IXFECTIO  US  DISEA  SES. 

was  found  to  be  alone  the  disease  manifested  an  evolution  similar 

to  that  observed  in  animals — i.  e.,  a  solid  tumor  constituted  the 
lesion.  Suppuration  is  not  produced  in  animals,  because  they  are 
less  sensitive  to  the  action  o(  pyogenic  agents. 

Therefore,  in  order  to  form  an  idea  of  the  lesions  created  by  the 
parasite  when  acting  alone,  actinomycosis  should  be  studied  in 
animals.  In  the  bovidse  the  disease  is  characterized  by  a  volum- 
inous tumor,  generally  located  in  the  lower  jaw  and  invading  the 
adjacent  muscles.  In  other  instances  it  begins  in  the  periosteum; 
the  bone  becomes  excavated  and  filled  with  morbid  matters.  The 
teeth  are  loosened,  and  mastication  is  impossible.  If  the  tongue 
is  invaded,  this  organ  becomes  hard  (holzzunge  (woody-tongue)  of 
German  authors)  and  the  animal  can  no  longer  use  it.  The  pharynx, 
respiratory  passages,  and  spine  may  also  be  involved. 

The  disease  is  seldom  generalized,  since  the  animals  are  killed 
too  soon.  Nevertheless,  a  few  cases  exist  in  which  the  evolution 
was  altogether  similar  to  that  of  acute  miliary  tuberculosis.  Such 
for  instance,  is  the  very  interesting  observation  made  by  Pflug  upon 
a  cow. 

Pathogenic  Streptothrix.  There  exist  certain  parasites  akin  to, 
but  not  identical  with,  actinomyces,  which  are  also  able  to  produce 
lesions. 

Aside  from  streptothrix  farcinosa,  which  is  not  pathogenic  for  man, 
we  may  mention  four  varieties  of  streptothrix  encountered  in  the 
human  species:  the  S.  Fozrsteri,  the  S.  asteroides  (Eppinger),  the 
S.  of  madura  foot,  and  the  S.  of  Poncet  and  Dor. 

Madura  foot  or  mycetom  is  an  affection  particularly  frequent  in 
India,  but  observed  also  in  America  and  Algeria.  Its  invasion  is 
characterized  by  a  painless  and  diffuse  swelling  of  the  integuments 
of  the  foot;  then  appear  little  tumors  which  are  at  first  hard,  but 
subsequently  soften,  break  down,  and  give  rise  to  a  sanious  pus 
containing  grayish,  yellowish,  or  black  granules.  The  lesion  always 
remains  local;  there  is  no  propagation  by  contiguity  or  by  embolism. 
The  affection  almost  invariably  terminates  in  death. 

This  parasite  is  easily  cultivated  in  vegetable  infusions  and  upon 
potatoes,  to  which  it  often  imparts  a  fine  red  color. 

Pseudoactinomycosis  of  Poncet  and  Dor  is  expressed  by  lesions 
analogous  to  those  of  true  actinomycosis,1  but  the  yellow  grains, 

1  Dor.  Une  nouvelle  mycose  &graines  jaunes.  Gazette  hebdomadaire,  1896.  Poncet. 
De  l'actinomycose  et  des  mycoses  cervico-faciales.     As*,  francaise  de  chirurgie,  1S9G. 


NODULAR  INFECTIONS.  319 

which  are  less  numerous,  are  much  larger  and  more  ea  ib  cm  hed. 
There  are  already  thirteen  observation  of  this  myco  i  reported, 
which  seems  not  to  he  of  very  rare  occurrence. 

Mycoses  in  Man.    Besides  the  streptothrix  there  are  plant*  capable 
of  producing  lesions  more  or  less  similar  to  those  of  actinomy© 
The  aspergillus  and  mucors  may  especially  be  mentioned. 

Paltauf  observed  a  pharyngolaryngeal  phlegmon  with  intestinal 
ulcerations  and  pneumonia;  in  all  the  foci  was  found  a  mucedina 
similar  to  the  mucor  corymbifer  of  Lichtheim. 

A  woman  expectorated  fragments  of  pulmonary  tissue  containing 
masses  of  aspergillus  (Rother).  In  the  case  of  a  young  man  who 
was  suffering  from  aspergillian  mycosis  of  the  trachea,  inhalations 
of  iodine  vapor  sufficed  to  cure  the  affection.  Wheaton  and  Etc  - 
published  similar  observations. 

If,  in  addition  to  these  clinical  facts,  we  bear  in  mind  the  experi- 
mental results  demonstrating  thai  various  forms  of  mucor  or  of 
aspergillus  may  be  pathogenic,  we  are  led  to  the  assumption  that 
a  good  many  infections  must  be  dependent  upon  more  highly  organ- 
ized parasites.  At  the  present  day  we  are  not  thoroughly  acquainted 
with  any  except  actinomycosis,  which  may,  therefore,  be  regarded 
as  the  type  of  a  whole  group. 

Tumors  and  Infections. 

We  do  not  intend  to  take  up  the  complex  and  as  yet  obscure 
history  of  tumors.  Although  convinced  of  their  parasitic  origin, 
we  must  frankly  acknowledge  there  are  no  irrefutable  facts  to 
support  this  opinion.  One  may  take  analogies  as  a  basis.  It  must 
be  recognized,  however,  that  most  of  the  observations  upon  tumors 
of  parasitic  origin  thus  far  reported  concern  sarcomatous  production.-. 
Sarcoma  simulates  tuberculosis  in  the  dog,  actinomycosis  in  bovidae, 
and  botryomycosis  in  the  horse.  On  the  other  hand,  it  is  un- 
doubtedly true  that  sarcomata  strikingly  resemble  inflammatory 
lesions;  there  is  structural  analogy,  at  times  identity.  The  oppo- 
nents of  the  parasitic  theory  would  readily  yield  this  group  of 
tumors,  but  emphatically  reject  the  infectious  nature  of  epithelioma. 

There  is  no  doubt  that  the  time  is  fast  approaching  when  tumors 
will  be  differently  classified.  Lesions  of  tuberculosis,  of  glanders, 
and  of  syphilis  which  twenty  years  ago  were  still  described  among 
the  neoplasms  by  eminent    histologists  (Yirchow.  among  others) 


321 '  INFECTIOUS  DISEASES. 

have  already  been  se1  aside.     The  same  is  true  with  actinomycotic 

tumors.  Employing  the  term  tumor  in  its  traditional  sense,  it  may 
be  said  that  there  arc  parasitic  tumors.  On  the  other  hand,  the 
relations  uniting  chronic  inflammations  with  adenomata,  and  these 
with  epitheliomata,  seem  to  prove  that  reactions  caused  by  the 
commonest  infectious  agents  may  evolve  toward  the  formation  of 
neoplasms.  Mechanical  irritations  of  tissues  act  in  the  same  manner. 
Traumatism,  contusion,  and,  above  all,  repeated  friction  and  irri- 
tation, may  lie  followed  by  the  development  of  tumors.  The  similar 
role  of  chemical  irritation  is  illustrated  by  the  development  of 
pulmonary  sarcoma  in  men  employed  in  arsenical  cobalt  factories 
(Hoerting  and  Hesse).  Finally,  larger  parasites  are  also  capable 
of  giving  rise  to  tumors.  Albarran  and  Bernard  had  the  opportunity 
to  study  a  vesical  tumor  presenting  the  appearance  of  epithelioma, 
which  appearance  was  due,  in  reality,  to  the  ova  of  bilharzia  hema- 
tobia  present.  With  Cadiot  and  Gilbert1  the  writer  observed,  in 
an  old  dog,  tumors  of  the  vulva  which  had  deformed  the  vagina 
and  perforated  the  wall  at  several  points.  Microscopic  examination 
showed  that  these  productions  were  formed  of  round  cells,  in  the 
midst  of  which  acarina  were  seen. 

Experimental  Tumors  of  the  Thyroid  Gland.  The  most  ordinary 
inflammations  may  likewise  give  rise  to  neoplastic  masses  in  animals. 
In  this  connection  we  have  reported  the  results  of  an  experiment 
made  in  conjunction  with  Dr.  Gamier.2 

On  May  9,  1898,  we  injected  five  drops  of  a  diluted  culture  of  the 
staphylococcus  aureus  into  the  carotid  artery  of  a  rabbit  so  as  to 
reach  the  thyroid  vessels.  Five  days  later  we  injected  the  same 
amount  of  the  same  culture  into  the  other  carotid.  This  rabbit 
survived  three  months,  until  August  11th.  It  bore  on  the  right 
side  of  the  neck  an  irregular  but  clearly  encapsulated  tumor  as 
large  as  a  walnut.  This  hard  tumor  had  the  appearance  of  a  sarcoma 
and  contained  in  its  interior  softer  caseous  masses.  It  represented 
the  right  lobe  of  the  thyroid  gland  extremely  developed.  The  left 
lobe  had  preserved  its  normal  form  and  connections,  but  looked 
enlarged. 

In  microscopic  sections  of   the  tumor  the  thyroideal  tissue  was 

1  Cadiot,  Gilbert,  and  Roger.  Les  tumeurs  malignes  chez  les  animaux.  La  presse 
mSdicale,  Jul}-  14,  1894. 

2  Roger  and  Garnier.  Recherches  exp^rimentales  sur  les  infections  thyro'idiennes. 
La  presse  medicale,  August   9,  1900. 


NODULAR  INFECTIONS.  321 

completely  unrecognizable;  nowhere  was  there  any  trace  of  lobule, 
vesicle,  or  colloid  substance.  This  tissue  was  made  up  of  collections 
of  epithelial  cells  withoul  any  orderly  arrangement,  between  which 
a  few  connective  tissue  bands  were  visible.  The  epithelial  cells 
appeared  to  be  profoundly  modified;  the  nuclei  were  very  large, 
vesicular,  irregular,  and  faintly  tinged  by  the  ordinary  dyes.  Large 
numbers  of  leucocytes  infiltrated  the  entire  tumor;  they  were  often 
disseminated  between  the  cells;  elsewhere  they  were  united  in  the 
shape  of  little  islands;  their  nuclei  were  small,  deeply  colored,  and 
contrasted  markedly  with  the  lighl  nuclei  of  the  epithelial  cells. 

The  left  lobe  presented  the  same  structural  alteration,  bul  had 
not  undergone  Hie  enormous  hypertrophy  noted  in  the  righl  one. 

It  was  quite  difficult  to  assign  a  place  in  nosology  to  this  morbid 
production.  In  reality  we  were  in  the  presence  of  a  genuine 
neoplasm,  and  the  groat  development  of  the  tumor  could  not  be 
attributed  solely  to  the  infiltration  by  leucocytes.  In  order  to 
produce  this  enormous  mass  the  epithelial  tissue  had  abundantly 
proliferated.  It  appears,  therefore,  that  the  cells  had  responded 
to  the  morbid  excitement  by  increased  activity,  resulting  in  con- 
siderable multiplication  of  the  epithelial  elements  and  hypergonosis 
of  tissue.  Later,  all  these  newly-formed  cells  degenerated,  necrotic 
foci  appeared  here  and  there,  and  leucocytes  wandered  in.  This,  then, 
was  a  case  of  true  inflammatory  neoplasm  in  process  of  degeneration. 

Attempts  to  Inoculate  Cancer.  If  tumors  could  be  successfully 
inoculated,  this  would  be  a  powerful  argument  in  support  of  the 
parasitic  theory.  The  facts  thus  far  reported  are  far  from  demon- 
strative. Although  it  seems  to  be  proved  that  cancer  is  inoculable 
from  one  part  to  another  part  of  the  organism  affected.  it>  trans- 
mission from  a  diseased  to  a  healthy  individual  is  doubtful,  in  spite 
of  a  few  observations  of  cancer  of  the  penis  in  men  who  had  had 
sexual  intercourse  with  women  suffering  from  uterine  cancer.  Ex- 
perimental pathology  furnishes  no  better  results  ;  thus  far  no  experi- 
menter has  succeeded  in  transmitting  human  cancer  to  animals,  nor 
from  animal  to  animal  of  similar  species.  The  only  positive  facts, 
those  of  Hanan  and  of  Moreau,  concerned  rats  and  mice.  According 
to  Menetrier's  remark,  inoculation  is  not  successful  except  when 
practised  upon  animals  of  the  same  family  in  which  cancer  has 
already  made  its  first  appearance,  and  from  that  moment  on  it 
affects  several  individuals.  This  is  practically  equal  to  the  grafting 
of  the  disease  into  the  individual  itself. 

21 


322  /  SFECTIO  US  DISEASES. 

Our  own  attempts,  repeated  a  great  number  of  times,  gave  no 
results.  We  inoculated  the  cancer  of  man  into  dogs,  rabbits,  and 
rats,  and  the  cancer  of  dog  into  dogs  and  rabbits.  The  inoculations 
w<  re  made  beneath  the  skin,  into  the  peritoneum,  and  peripheral 

veins:  lastly,  in  view  of  the  frequency  of  secondary  cancer  in  the 
liver,  we  made  inoculations  through  the  portal  vein.  We  constantly 
failed.  We  failed  even  when  we  endeavored  to  inoculate  into  can- 
cerous dogs  fragments  of  their  own  tumors.  In  two  cases  we  believed 
we  obtained  positive  results.  In  one  of  them,  however,  the  tumor 
found  in  the  spleen  of  an  inoculated  dog  did  not  present  the  same 
histological  characters  as  the  mammary  neoplasm  which  had  served 
for  the  experiment.  In  the  other  instance,  the  lesions  presented  the 
macroscopic  characters  of  cancer,  but  were  in  reality  dependent  upon 
tuberculosis. 

These  two  observations  compel  us  to  regard  as  doubtful  the  old 
observations  and  all  those  in  which  no  careful  study  of  the  histological 
and  bacteriological  characters  of  the  lesions  were  made. 

Negative  results,  however,  do  not  warrant  denial  of  the  parasitic 
nature  of  tumors.  They  only  suggest  modification  of  experimental 
methods,  since  they  demonstrate  that  the  problem  will  not  be  solved 
by  merely  multiplying  inoculations  according  to  usual  procedures. 


m 


(II  A  PTEB    X  I. 
CELLULAR  DEGENERATIONS. 

le  of  Toxins  in  Hi"  Development  of  Cellular  Degenerations.  Study  of  tli<-  Different 
Varieties  of  Degenerations.  Cloudy  Swelling.  Qranulo-albuminoui  Degenera- 
tion, Granulo-fatty  Degeneration.  Fattj  Degeneration.  Amyloid  Degeneration. 
Pigmentary  Degeneration. 

The  description  which  has  been  given  <>!'  inflammatory  phenomena 
has  shown  what  arc  the  reactions  excited  a1  the  point  attacked  by 
infectious  agents.  The  purpose  of  these  reactions  is  to  circumscribe 
the  lesion  and  to  oppose  (he  diffusion  of  microbes  and  toxins.  Unfor- 
tunately, the  barrier  is  too  often  inadequate:  the  microbes  and  espe- 
cially the  toxins  succeed  in  impregnating  the  organism  and  produce 
various  general  manifestations. 

A  local  lesion,  even  when  circumscribed,  permits  the  diffusion  of 
substances  which  impregnate  the  surrounding  tissues.  In  absct 
the  liver,  for  instance,  if  the  local  lesion  is  intense  and  of  long  stand- 
ing, secondary  alterations  occur  in  the  hepatic  cells;  in  some  cases  the 
cells  in  immediate  contact  with  the  focus  are  affected;  in  other 
instances  the  whole  gland  suffers.  These  secondary  changes,  how- 
ever, differ  from  the  lesions  produced  at  the  primary  focus.  The 
changes  observed  are  not  inflammatory  alterations,  but  degenera- 
tions. 

Although  cellular  degenerations  often  predominate  in  the  part 
primarily  attacked,  the  process  may  in  some  cases  gradually  involve 
other  tissues  or  organs.  A  suppuration  localized  in  a  bone  or  joint 
may  thus  be  complicated  with  fatty  or  amyloid  degeneration  of  the 
principal  viscera.  An  important  role  was  once  attributed  to  hyper- 
thermia, insufficient  supply  of  oxygen,  respiratory  and  digestive 
disorders  in  the  genesis  of  steatosis.  It  is  at  present  known  that 
these  pathogenic  factors  are  of  little  importance:  the  true  cause  of 
the  morbid  events  is  found  in  the  diffusion  of  toxins. 

The  first  stage  of  cellular  degeneration  consists  in  cloudy  swelling. 
The  cells  are  swollen  and  filled  with  an  albuminous  or  serous  fluid 
holding  small  granules  in  suspension.  The  latter  present  two  stages : 
at  first,  there  is  granulo-albuminous   degeneration  ;   later,  granulo- 


324  l  -V/  'IX ' TIO  US  DISEASES. 

fatty  degeneration.  In  the  former  case  acetic  acid  swells  the  gran- 
ules and  then  dissolves  them;  in  the  latter  instance  the  granules  are 
colored  dark  by  osmic  acid.  This  morbid  state  is  observed  in  a  great 
number  of  inflammations;  it  affects  the  protoplasm  and  may  involve 
the  nucleus  and  nucleolus  of  the  cells. 

At  a  more  advanced  stage  we  find  fatty  degeneration,  properly 
so  called,  or  steatosis.  This  process,  which  plays  a  notable  role  in 
pathology,  must  not  be  confounded  with  fatty  infiltration,  which  is 
observed,  for  instance,  in  obesity.  In  the  case  of  fatty  infiltration 
there  is  simple  deposition  of  fat  in  the  interior  of  the  cell ;  the  proto- 
plasm may  be  pushed  aside,  but  its  activity  is  not  appreciably  dis- 
turbed. On  the  other  hand,  in  the  case  of  steatosis  or  fatty  degen- 
eration the  protoplasm  itself  is  transformed  into  fat.  Under  the 
influence  of  nutritional  disturbances  the  proteid  substance  suffers  a 
peculiar  metamorphosis;  hence  the  physiological  function  of  the 
element  is  profoundly  affected  or  even  completely  lost. 

Mucoid  or  colloid  degeneration  is  observed  in  the  epithelial  cells. 
It  is  characterized  by  the  deposition  of  mucinoid  substance  in  the 
interior  of  the  protoplasm.  This  may  be  compared  to  vacuolar 
degeneration  in  which  vacuoles  appear  to  be  present  in  the  cell. 
This  phenomenon  is  in  reality  due  to  the  presence  of  small  cysts 
filled  with  an  albuminoid  substance.  In  colloid  degeneration  the 
material  elaborated  in  the  diseased  cells  may  be  expelled.  If  it  enters 
an  excretory  duct  it  will  be  eliminated  from  the  system.  Such,  for 
example,  is  what  occurs  in  the  kidney;  the  colloid  masses  exuded 
from  the  cells  unite,  coalesce,  and  form  cylinders  which  are  detected 
in  the  urine  by  microscopic  examination.  When  the  substance  is 
retained  at  the  point  of  elaboration  it  gives  rise  to  the  development 
of  more  or  less  voluminous  cysts.  Thus  are  explained  the  cystic 
degenerations  of  the  kidney  and  liver,  the  formation  of  colloid  cysts 
in  the  thyroid  gland,  etc.  As  the  same  process,  however,  may  like- 
wise affect  pathological  cells,  cysts  may  be  produced  in  ttimors.  The 
ovarian  cyst,  for  instance,  is  looked  upon  as  an  epithelioma  charac- 
terized by  colloid  degeneration. 

Another  important  variety  of  degeneration  is  represented  by  hya- 
line degeneration.  It  is  essentially  characterized  by  the  production 
of  refractive,  homogeneous  masses.  It  is  frequently  encountered  in 
cases  of  nephritis,  in  inflammation  of  the  ovary,  and  in  tuberculosis ; 
it  is  not  rare  in  the  small  aneurisms  found  in  the  walls  of  tubercular 
cavities. 


CELLULAR  DEQENERA  TI0N8.  326 

Parallel  with  hyaline  degeneration  may  be  placed  transparent 
degeneration,  observed  by  Hanoi  and  Gilbert  in  the  liven  of  pel 
dead  of  cholera.    The  protoplasm  of  the  hepatic  cells  become   com- 
pletely transparent,  Lhe  nucleus  alone  persi  ting. 

Lastly,  Zenker's  waxy  degeneration  is  generally  considered  to  1^; 
the  same  as  hyaline  degeneration.  K  is  an  alteration  attacking  the 
striated  muscles.  If  was  firsl  encountered  in  typhoid  fever,  and 
subsequently  observed  in  a  greal  number  of  infections.  [1  ma] 
be  experimentally  produced  by  tetanization  of  the  muscles.  It  is 
essentially  characterized  by  swelling,  hyaline  metamorphosis,  and 
fragmentation  of  the  muscular  I  issue 

There  is  no  accurate  knowledge  concerning  the  nature  of  hyaline 
degeneration.  It  lias  been  noticed  that  the  substance  infiltrating 
the  cells  resists  reagents.     This  fact  is  one   of   the  n  hy  if 

is  compared  to  another  variety  of  degeneration,  viz.,  amyloid  degen- 
eration. 

Hyaline  degeneration  must  not  be  confounded  with  glassy  degen- 
eration. The  latter  is  essentially  characterized  by  a  transformation 
of  the  cell,  all  parts  of  which  lose  their  histochemical  properties. 
The  protoplasm,  nucleus,  and  nucleolus  are  no  longer  differentiated. 
It  would  seem,  therefore,  that  this  process  should  be  identified  with 
fibroid  degeneration  or  coagulation  necrosis.  This  is  a  process  sim- 
ilar to  the  one  presiding  over  the  coagulation  of  organic  substances 
containing  fibrin. 

It  is  often  stated  that  glassy  degeneration  is  the  first  stage  of 
caseous  degeneration.  In  fact,  it  seems  certain  that  the  cells  are 
attacked  by  coagulation  necrosis  before  undergoing  the  transforma- 
tion or,  one  might  almost  say,  the  special  fermentation  which  ends 
in  their  caseation. 

There  still  remains  pigmentary  degeneration,  characterized  by  a 
transformation  of  the  protoplasm.  It  should  not  be  confounded 
with  pigmentary  infiltration  due  to  a  simple  accumulation  of  pig- 
ments transported  to  the  cell.  The  difference  here  is  the  same  as 
that  between  fatty  degeneration  and  fatty  infiltration. 

A  sclerotic  degeneration  is  also  often  spoken  of.  This  is  the  process 
which  has  already  been  described  as  a  mode  of  repair,  a  true  cica- 
trization. Connective  tissue  develops  in  order  to  replace  the  cells 
that  have  degenerated  or  disappeared.  The  cicatrized  tissue  is  some- 
times infiltrated  with  calcareous  salts :  this  process  is  known  as  cal- 
careous degeneration. 


326  INFECTIOUS  DISEASES. 

Causes  of  Cellular  Degenerations.    Although  degenerations  differ 

in  their  anatomical  and  clinical  expression  and  occur  under  condi- 
tions peculiar  to  each  of  them,  and  also  have  a  dissimilar  significance 
and  evolution,  the  numerous  varieties  above  described  are,  never- 
theless, related  by  analogous  etiological  and  pathogenic  conditions. 

Cellular  degenerations  always  express  some  nutritional  distur- 
bance. The  latter  may  depend  upon  three  distinct  causes:  1.  Defi- 
cient supply  of  materials  destined  for  nutrition;  2,  vitiation  of  the 
interstitial  plasma — i.  e.,  an  intoxication  disturbing  nutritive  metab- 
olism: 3,  disturbance  or  suppression  of  the  functions  of  the  cell. 

At  the  head  of  the  first  group  is  naturally  placed  starvation.  It 
has  been  demonstrated  by  a  great  number  of  observations  and  experi- 
ments that  suppression  of  alimentation  is  speedily  followed  by  cellu- 
lar degeneration,  under  the  form  of  fatty  metamorphosis. 

The  same  results  are  observed  when  the  blood  is  altered,  either 
because  it  no  longer  brings  to  the  cells  a  sufficient  amount  of  aliment 
or  because  it  is  not  charged  with  the  requisite  quantity  of  oxygen. 
The  former  condition  is  realized  when  the  blood  mass  is  lessened,  for 
example,  as  the  result  of  profuse  hemorrhages ;  the  latter  occurs  when 
the  blood  corpuscles  are  altered  or  decreased  in  number,  to  wit,  when 
a  local  or  a  general  anemia  exists. 

It  is  stated  that  accumulation  of  carbonic  acid  produces  the  same 
effect  as  inadequate  supply  of  oxygen,  and  this  explains  the  occur- 
rence of  degeneration  in  cases  of  venous  obliteration  or  cardiopul- 
monary insufficiency.  In  this  case,  however,  the  process  is  rather 
one  of  intoxication,  and  we  are  thus  led  to  the  consideration  of  our 
second  group. 

It  is  known  that  a  great  number  of  mineral  poisons  give  rise  to 
cellular  degenerations.  It  will  suffice  to  mention  arsenic  and  espe- 
cially phosphorus. 

The  same  is  true  of  cases  of  endogenous  intoxication.  Whether 
the  question  be  one  of  noxious  products  developed  under  the  influence 
of  cellular  life,  or  one  of  substances  formed  by  bacteria  normally  or 
accidentally  inhabiting  our  bodies,  the  result  is  the  same.  Let  us 
assume,  for  example,  the  condition  to  be  one  of  increased  gastro- 
intestinal putrefaction;  as  a  result  of  the  absorption  of  excessive 
amounts  of  toxins  formed,  a  degeneration  of  the  hepatic  and  renal 
cells  will  occur,  and  this  may  prove  to  be  the  beginning  of  a  cirrhosis 
or  a  nephritis.  A  good  many  cases  of  Bright 's  disease  are  due  to  no 
other  origin. 


CELLULAR  DEGENERATIONS. 

What  is  done  by  the  toxins  of  putrefaction  i    more  fully  realized 
by  the  toxins  of  pathogenic  agents.     The  numerou    varieti* 
degeneration  above  described  are  encountered  in  the  eour  e  oi  infec- 
tious diseases    from  cloudy  swelling  to    teato  i  .  coagulation  i. 
sis,  and  amyloid  degeneral  ion. 

We  have  stated  thai  degeneration  may  be  referable  to  uppr<  wion 
or  disorder  of  cellular  activity.  An  important  distinction  musl  be 
in  (rod i iced  at  this  point,  [n  cases  of  simple  lack  of  function  atrophy 
occurs,  but  not  degeneration.  The  muscles  of  an  individual  who 
remains  inactive  diminish  simply  in  volume;  when,  for  instance,  a 
limb  is  placed  in  an  immovable  apparatus,  il  atrophies  bul  does  uol 
degenerate.  The  same  is  true  of  glands  which  remain  a1  rest.  On 
the  other  hand,  degeneration  is  produced  when  lack  of  activity 
results  from  functional  disturbance.  It'  a  muscle  or  a  gland  remains 
at  rest  because  its  nutrient  vessels  are  altered  or  because  the  nervous 
cells  controlling  the  functions  or  the  nerves  transmitting  the  impulses 
are  affected,  it  is  not  atrophy  bul  degeneration  thai  occurs.  Thus, 
section  of  a  nerve  does  not  act  upon  the  muscle  through  the  immo- 
bility resulting  therefrom;  the  phenomena  are  more  complex — the 
necessary  stimulus  is  suppressed  and  degeneration  seems  again  if  be 
connected  with  a  trophic  disturbance. 

Without  wishing  to  even  briefly  study  the  different  varieties 
degenerations,  it  may  be  well  to  give  some  complementary  informa- 
tion concerning  those  most  frequently  encountered  and  which  have 
thus  far  only  been  alluded  to:  fatty  degeneration  and  amyloid  degen- 
eration. We  shall  then  present  some  considerations  relative  to  pig- 
mentary degeneration. 

Fatty  Degeneration. 

Fatty  degeneration  or  steatosis  is  essentially  characterized  by  a 
fatty  transformation  of  the  nitrogenous  substance  which  enters  into 
the  constitution  of  anatomical  elements.  As  already  stated,  this 
should  be  carefully  distinguished  from  fatty  infiltration,  which  is  in 
reality  a  cellular  obesity.  In  the  latter  case  fat  is  stored  up  in  the 
cellular  membrane  and,  in  order  to  make  room  for  it,  the  protoplasm 
is  slightly  pushed  aside.  There  is  addition  of  a  new  substance,  and 
not  metamorphosis  of  one  already  existing. 

Fatty  degeneration  may  be  established  at  once  or  follow  another 
variety,  such  as  granular  degeneration,  cloud}-  swelling,  or  albumin- 
ous infiltration.     Under  the  microscope,  in  specimens  fixed  by  means 


328  INFECTIOUS  DISEASES. 

of  osmic  acid,  fat  appears  in  the  form  of  small,  black  granules, 
isolated  or  united  in  masses,  and  particularly  profuse  around  the 
nucleus.  This  steatosis  is  frequent  in  the  liver,  kidneys,  myocar- 
dium, and  muscles.  It  originates  under  the  most  varied  conditions. 
Nutritive  disturbances  caused  by  high  temperatures  are  considered 
important  etiological  factors,  and  are  supposed  to  explain  the  fre- 
quency of  steatosis  in  infections.  It  should  be  remarked,  however, 
that  in  this  instance  the  problem  is  a  highly  complex  one,  since 
i  he  alterations  maybe  more  easily  accounted  for  by  a  production 
of  toxins  than  by  thermal  elevation.  Nevertheless,  the  latter 
pathogenic  condition  may  also  be  taken  into  account,  because  fatty 
degeneration  has  been  induced  experimentally  in  animals  whose 
temperature  was  raised  by  prolonged  confinement  in  an  oven. 
The  alteration  is  supposed  to  be  due  to  a  lack  of  oxidation,  since, 
under  the  influence  of  high  temperature,  the  red  blood  corpuscles 
take  up  less  oxygen  than  under  normal  conditions. 

The  same  explanation  may  be  applied  to  other  etiological  condi- 
tions. The  steatosis  manifesting  itself  in  the  course  of  infections  and 
poisonings  may  be  attributed  to  deficient  oxidation. 

Finally,  steatosis  occurs  when  an  organ  is  rendered  inactive  in 
consequence  of  suppression  of  nervous  excitation,  because  metabo- 
lism does  not  progress  in  a  normal  manner.  Nervous  influence  is 
indispensable  for  the  regular  performance  of  nutrition.  When  this 
influence  fails,  oxidation  diminishes  and  fatty  degeneration  is  pro- 
duced. The  more  active  an  organ  is,  the  greater  are  its  demands 
for  oxygen;  consequently,  if  the  supply  of  this  gas  be  diminished, 
degeneration  will  first  affect  those  parts  which  manifest  the  greatest 
physiological  activity.  Among  the  muscles  the  myocardium  is  first 
attacked,  then  the  diaphragm ;  among  the  glands,  the  liver  and  the 
kidneys. 

It  is  not  superfluous  to  note  that  steatosis  occurs  when  there  is 
diminution  but  not  suppression  of  oxidations.  Stricture  of  an  artery 
gives  rise  to  fatty  degeneration;  its  obliteration,  if  not  partially  com- 
pensated by  collateral  circulation,  results  in  necrosis.  Suppression 
of  oxidation  ends  in  the  death  of  the  cellular  elements. 

Amyloid  Degeneration. 

Amyloid  degeneration  was  described  by  Rokitansky  (1842)  under 
the  name  lardaceous  degeneration,  by  Christensen  (1844)  under  the 
designation  waxy  degeneration.    Virchow  (1853)  gave  it  the  name 


OELLULA  i:  DEGENERATIONS.  329 

it  now  bears.     In  1858  and  LS59  Kekule  and  Schmidl  showed  'lint 
amyloid  I  issue  is  not,  as  mighl  be  assumed,  an  amylaceou     ubstance ; 

it  is  :in  albuminoid     /.  c.,  ;i  nitrogenou      lib  tance. 

In  whatever  locality  ii  may  be  found  il  i    recognized   by  mean 
of  certain  very  simple  reactions.     Under  the  influence  of  the  iodo- 
iodide   test  it  gives  a  mahogany-red  color,  which  becomes  violet-red 
on  addition  of  sulphuric  acid.    On  contacl   with  methyl-violel   i' 
becomes  red. 

Amyloid  substance  is  perhaps  normally  mel  with  in  certain  parte 
of  the  organism.  II  often  constitutes  an  epiphenomenon  in  the 
course  of  the  most  varied  affections,  notably  of  nephritis.  In  certain 
cases  it  may  be  so  widely  distributed  thai  amyloidism  i-  the  prin- 
cipal phenomenon.  Cohnheini  has  reported  cases  in  which  amyloid 
degeneration  invaded  the  organism  withoui  any  cause  to  explain  this 
alteration.  Such  an  event  is  exceptional.  Amyloid  degeneration 
nearly  always  occurs  in  the  course  of  infectious  diseases  that  are 
liable  to  induce  cachectic  conditions,  such  as  tuberculosis,  syphilis, 
and  multiple  suppurations. 

Tuberculosis  stands  at  the  head  of  the  list.  Amyloidism  is  com- 
monly observed  in  patients  who  have  pulmonary  cavities,  extensive 
lesions  of  the  intestine,  articular  or  osseous  suppurations,  necrosis, 
and  caries.  The  foci  nearly  always  communicate  with  the  exterior. 
Next  comes  syphilis,  particularly  inherited  syphilis.  The  spleen  is 
the  organ  chiefly  affected.  Suppurations  of  long  standing  may  also 
give  rise  to  amyloid  degeneration.  Sometimes  arthropathies  or 
osseous  suppurations;  at  other  times  visceral  abscesses,  dilatation  of 
the  bronchi,  or  multiple  abscesses  of  the  skin,  are  the  causative  fac- 
tors. Lastly,  among  the  rarer  causes,  Ave  may  cite  cancer,  especially 
ulcerated  cancer,  and  malaria. 

This  etiological  multiplicity  shows  that  individuals  of  all  ages  may 
be  attacked.  Amyloidism,  however,  is  particularly  frequent  among 
men  and  at  the  middle  period  of  life,  viz.,  between  twenty  and 
thirty  years. 

Animals  are  not  exempt  from  this  degeneration.  As  in  man.  it 
is  encountered  in  tuberculosis  and  chronic  suppurations.  Krawkow 
succeeded  in  producing  it  experimentally.  It  is  constantly  observed 
in  tubercular  pheasants,  in  the  livers  of  which  the  tubercles  are 
surrounded  by  a  zone  of  connective  tissue  infiltrated  with  amyloid 
substance. 

It  is  at  present  universally  agreed  that  amyloid  matter  should  be 


330  INFECTIOUS  DISEASES. 

classed  as  of  nitrogenous  origin,  hut  the  mechanism  presiding  over 
its  formation  is  as  yet  unknown.  Wagner  holds  this  substance  to 
be  intermediate  between  albumins  and  fats,  and  this  would  explain 
the  frequent  coexistence  of  amyloid  and  fatty  degenerations.  Reck- 
linghausen believes  a  homogeneous  matter  is  exuded  from  the  cells 
which  coagulates  on  contact  with  the  interstitial  fluids.  In  the 
opinion  of  Ziegler,  the  diseased  cells  are  unable  to  utilize  the  albumins 
escaping  from  the  vessels;  hence  the  albumins  undergo  a  special 
metamorphosis. 

At  all  events,  it  is  certain  that  amyloid  degeneration  is  closely 
related  to  fatty  degeneration,  since  it  is  produced  under  the  same 
conditions,  and  must,  therefore,  be  considered  as  connected  with  dis- 
turbance of  albuminous  nutrition. 

Amyloid  degeneration  affects  the  vessels  and  the  connective  tissue 
in  a  predominant  if  not  an  exclusive  manner.  In  the  arteries  it 
begins  in  the  inner  coat,  sparing  the  endothelium;  it  is  especially 
marked  in  the  middle  coat.  It  extends  to  the  capillaries,  which  it 
transforms  into  vitreous,  homogeneous  tubes  lined  with  epithelial 
cells  which  remain  intact. 

When  it  affects  the  organs  it  appears  in  three  different  macroscopic 
forms.  The  whole  or  the  greater  part  of  the  organ  is  invaded;  the 
tissue  becomes  homogeneous,  semitransparent,  and  larclaceous.  At 
other  times  the  process  is  limited  to  small  foci  presenting  the  appear- 
ance of  sago  grains.  Finally,  the  lesions  may  be  minute  and  recog- 
nizable only  under  the  microscope  or  by  transmitted  light  in  thin 
sections  treated  with  the  usual  reagents. 

The  liver,  which  is  the  organ  most  frequently  attacked,  becomes 
considerably  enlarged;  it  appears  pasty,  larclaceous,  and  almost 
bloodless.  Under  the  microscope,  infiltration  of  the  capillaries, 
the  hepatic  artery,  more  rarefy,  of  the  portal  vein,  is  found.  As  to 
the  changes  in  the  hepatic  cells  themselves,  discussion  is  still  open. 
Some  authors  assert  that  degeneration  occurs;  others  contend  that 
the  vitreous  masses  encountered  are  not  altered  cells,  but  amyloid 
masses  exuded  from  the  vessels. 

The  localization  is  analogous  in  the  other  organs.  In  the  spleen 
it  is  mainly  deposited  in  the  Malpighian  corpuscles.  In  the  kidneys 
it  is  found  in  the  vessels,  glomeruli,  connective  tissue,  and  the  walls 
of  the  uriniferous  tubules.  The  epithelial  cells  are  often  altered,  but 
never  amyloid.  We  may  also  mention  the  amyloid  degeneration 
occurring  in  the  lymphatic  glands,  in  the  intestinal  mucous  mem- 


CELLULAR  DEQENEBA  TI0N8.  331 

brane,  and  the  heart,  where  the  mu  cle  cells   may  be  involved 

(Letulle  and  Nicolle). 

When  amyloid  degeneration  is  localized  it  does  nol  vlw 
any  special  disturbances.    Thus,  in  parenchymatous  nephritis,  in 
which  it  is  almosl  constant,  H  is  qo1  expressed  by  any  appreciable 
manifestation. 

When  ii  is  extensive  i1  produces  a  certain  oumber  of  phenomena 
which  vary  according  to  its  predominance  in  thif  or  thai  organ.  The 
first  indications  are  paleness  of  the  pal  ienl  paleness  of  the  skin  and 
mucous  membranes  and  loss  of  strength.  Examination  of  the 
abdomen  reveals  considerable  hypertrophy  of  the  liver  and  spleen; 
diarrhea  is  of  frequent  occurrence;  the  urine  is  remarkable  for  its 
abundance,  pale  color,  and  the  greal  amounl  of  albumin  which  it 
contains,  at  least  in  certain  cases. 

Though  a  Fatal  termination  is  the  rule,  recovery  is  possible.  The 
patient  overcomes  the  cause  that  has  produced  the  degeneration,  and 
the  latter  subsides  and  finally  disappears.  Cohnheim,  who  has  laid 
stress  upon  this  evolution,  cites  the  following  experimeni :  Fragments 
of  amyloid  tissue  when  introduced  into  the  peritoneal  cavity  of  an 
animal  are  rapidly  absorbed.  According  to  him,  it  must  be  conclui  led 
that  absorption  of  this  substance  may  occur  in  the  human  organism. 
This  experience  is  interesting,  since  amyloid  matter  is  very  resistant. 
It  is  not  altered  when  submitted  to  artificial  digestion  with  pepsin 
and  hydrochloric  acid.  Indeed,  these  are  the  means  generally  em- 
ployed for  its  preparation. 

Pigmentary  Degeneration. 

There  are  cases  of  simple  pigmentary  infiltration  and  cases  of  ]  lig- 
mentary  degeneration.  The  cells  may  be  charged  with  coloring- 
matters,  particularly  the  leucocytes,  which  are  often  loaded  with 
carbon,  even  under  normal  conditions.  In  other  cases  The  cells  may 
be  infiltrated  with  more  or  less  modified  blood  pigment  derived  from 
former  hemorrhage.  Finally,  various  black  pigments,  apparently 
derived  from  the  blood,  may  accumulate  in  certain  anatomical 
elements  without  disturbing  their  function.  In  the  case  of  pigmen- 
tary degeneration,  on  the  contrary,  cellular  alterations  are  found 
which  account  for  the  disorders  observed  during  life. 

Pigmentary  degeneration,  which  is  chiefly  observed  in  malaria,  is 
essentiallv  characterized  bv  the  accumulation  within  the  cells  of  an 


:):)'2  INFECTIOUS  DISEASES. 

okra  matter  (pigment  ocre  of  Kelsch  and  Kiener,  rubigin  of  Auscher 
and  Lapique),  which  has  the  property  of  turning  black  under  the 
action  of  ammonia  sulphydrate3  or  blue  on  addition  of  potassium 
ferrocyanide  and  dilute  hydrochloric  acid.  The  latter  reaction,  which 
is  very  sensitive,  is  currently  employed  in  histology.  In  preparations 
thus  treated  it  may  be  seen  that  the  pigment  invades  the  protoplasm, 
pushes  it  aside,  atrophies  the  nucleus  and  causes  disappearance  of 
the  latter.  All  organs  are  not  equally  liable  to  attack.  As  is  always 
the  case,  the  frequency  of  the  lesions  is  in  proportion  to  functional 
activity.  The  liver  is  the  organ  most  frequently  invaded;  next  come 
the  kidneys,  then  the  myocardium  and  the  pancreas. 


Oil  A  PTEB    XII. 
GENERAL  REACTIONS    FEVER. 

Functional  Synergies  and  Morbid  Sympathies.  Contiguity  of  Organs.  Vascular  Con- 
ncciions.  Hole  of  Kmlioli  m  I  Kile  of  Humeral  Modifications.  Nervoui  Connec* 
tions.  Fever.  Definition.  Thermometry  and  Calorimetry.  Mechanism.  Ner- 
vous and  Toxic  Fevers.  SiL'ni  lii-.-i  hit  oi'ri,iii-  and  Sweating.  Feveri  b  Reaction 
of  the  Organism.  Hypothermia  Produced  I.;.-  Toxins.  Final  Hypothermia  in 
Animals.  Persistent  Hyperthermia  in  Man.  Causet  of  ilii-  Difference.  Produc- 
tion of  Heat  in    l'cMis  by  Retention.     State   of  Oxidations.    The  Thermogenic 

Power  of  1  lie  Blood.      liole  of    (In-   Liver,   Kidney,  Mini    I.iihl'-    in   t  Ik-  Production  of 

Fever.     Role  of   the    Muscles   and    Nervous  System.     Therapeutic   Deductions. 
Characters  of  Feverin  Some  Infections.    Semiological  Value  of  the  Thermal  Course. 

Functional  Synergies  and  Morbid  Sympathies. 

The  various  parts  of  the  system  an-  so  closely  unite.  I  bysynergies 
that  it  is  impossible  for  a  lesion  to  remain  absolutely  local.     On 

superficial  examination  the  disturbances  may  a] (pear  to  be  confined 
to  a  part  of  the  organism:  in  reality,  however,  it  necessarily  gives 
rise  to  a  great  number  of  modifications  in  the  entire  economy.  Reac- 
tions may  be  more  or  less  marked,  at  times  even  imperceptible; 
nevertheless  they  exist. 

It  is  highly  interesting  to  investigate  the  mechanism  through 
which  the  lesions  of  an  organ  affect  the  rest  of  the  system. 

The  connections  existing  between  the  various  parts  of  the  organism 
suggest  the  following  classification  of  the  pathogenic  processes  of  a 
secondary  order : 

1.  Functional  synergies. 

2.  Contiguity  of  organs. 

3.  Vascular  connections. 

4.  Nervous  connections. 

Referring  for  the  general  study  of  secondary  pathogenic  proce  --  - 
to  the  article  which  the  author  has  devoted  to  this  subject.1  he  will 
Consider  only  their  importance  in  infectious  diseases. 

Functional  Synergies.  As  the  result  of  physiological  researches 
and  clinical  observations,  parts  which  were  separated  by  anatomical 

1  Roger.  Les  processus  pathogeniques  de  deuxieme  ordre.  Traite  de  pathologie 
generate,  published  by  Prof.  Bouchard,  Paris.  1899,  vol.  iii.  p.     v 


334  INFECTIOUS  DISEASES. 

study  have  been  united.  Thus  are  formed  physiological  unities, 
acting  in  harmony  and  working  together  to  insure  the  same  function. 
For  example,  the  motor  cell,  the  muscle,  and  the  nerve  thai  unites 
them  represent  a  whole  from  the  functional  standpoint.  Pathology 
agrees  with  physiology  by  showing  that  the  alteration  of  one  of  these 
pans  effectively  influences  the  others.  We  cannot,  however,  expand 
on  these  facts,  since  they  present  nothing  peculiar  in  infections.  When 
alterations  of  an  organ  induce  lesions  in  another  the  process  is  an 
autogenous  one  which  acquires  no  particular  character  from  the 
acting  cause.  Thus,  destruction  of  the  cells  in  the  anterior  horn  of 
the  spinal  cord  results  in  atrophy  of  the  corresponding  muscular 
fibres.  Here  is  a  striking  example  of  morbid  sympathy  correspond- 
ing exactly  to  a  functional  synergy.  However,  whatever  the  eause 
that  has  produced  the  cellular  lesion  may  be,  the  muscle  will  degen- 
erate. Likewise,  when  lesions  of  the  liver  produce  consecutive 
lesions  in  the  kidneys,  the  process  that  has  acted  upon  the  hepatic 
gland  imparts  no  particular  character  to  the  renal  lesion.  It  is  not 
superfluous  to  refer  to  these  facts,  for  they  explain  a  great  variety 
of  symptoms  occurring  in  the  course  or  in  consequence  of  infectious 
diseases. 

Contiguity  of  Organs.  It  will  suffice  to  recall  for  a  moment  the 
anatomical  positions  and  mutual  relations  of  organs  in  order  to 
comprehend  how  lesions  developing  in  one  of  them  may  mechani- 
cally affect  the  others.  A  purulent  focus  produced  in  one  part 
compresses  the  adjacent  parts  and  produces  in  them  various  dis- 
turbances which  may  be  transitory — i.  e.,  disappear  with  the  lesion 
which  caused  them — or  may  survive  it  and  run  an  independent 
course  of  evolution. 

If  the  compressing  organ  is  the  seat  of  an  inflammatory  affection, 
notably  a  suppurating  or  gangrenous  lesion,  it  may,  in  addition  to 
the  mechanical  influence,  exert  a  specific  action.  An  inflamed  tissue 
often  gives  rise  to  paralysis  in  subjacent  parts.  Stokes  long  ago 
proved  this  fact  as  regards  the  diaphragm  in  cases  of  purulent  pleu- 
risy. Likewise,  a  phlegmonous  angina  may  cause  paralysis  of  the 
palate.  In  certain  rare  instances  an  acute  pericarditis  may  produce 
paralysis  of  the  myocardium.  What  is  produced  in  the  striated 
muscles  is  likewise  observed  in  the  non-striated;  such  is  the  case  in 
gastrointestinal  paralysis  occurring  in  peritonitis. 

Are  these  paralytic  phenomena  due  to  the  special  influence  of  the 
inflamed  tissue,  or  are  they  the  result  of  the  action  of  soluble  products 


GENERA  L  REACTIONS    FEVER. 

secreted  by  the  pathogenic  agenl  ?     It  i    at  present  iinpot  ibl< 
answer  these  questions.    They  requin  experimental  investigatii 

Vascular  Connections.    By  acting  upon  the  heart,  disturbing 
function,  altering  its  tissues,  or  by  creating  valvular  lesions,  infec 
lions   produce    profound    modification):    in    the   blood   circulation, 
and   thus  give  rise  to  a  series  of   disorder    throughout   the  entire 
system. 

Role  of  Embolism,  li  is  through  the  vascular  >-i'in  particularly 
that  infectious  foci  produce  lesions  in  distant  parts.  Ve  -•■]-  trav- 
ersing diseased  parts  are  often  obliterated  either  because  microbee 
penetrate  into  them  or  because  toxins  diffuse  and  give  rise  to  toxic 
endarteritis  or  endophlebitis.  The  latter  hypothesis  is  supported  by 
the  fact  that  emboli  are  no1  necessarily  infective;  they  may  ad 
mechanically.  It  is,  therefore,  possible  to  observe  fibrinous  emboli 
exuded  from  an  obliterated  vein  in  contact  with  a  purulent  focus;  in 
other  instance's  fatty  emboli  occur,  originating  from  an  a 
myelitis. 

Besides  mechanical  emboli,  there  arc  animate  one-  which  have  a 
highly  important  bearing  on  our  subject,  since  they  account  for  the 
extension  and  generalization  of  a  great  number  of  lesions.  Lot  us 
take,  for  example,  actinomycosis.  The  primary  focus  may  give  rise 
to  secondary,  sometimes  multiple,  lesions,  which  in  some  cases  are 
sufficiently  numerous  to  suggest  pyemia.  The  same  is  true  of  cast  e 
of  aphtha;  and  this  result  is  comprehensible,  since  AYagner  has  shown 
that  the  oidium  sends  out  prolongations  into  the  vessels  of  the 
mucous  membrane.  In  this  way  is  explained  the  formation  of  vis- 
ceral foci,  such  as  have  been  recorded  by  Zenker  and  Ribbert. 

It  is  in  generalization  of  infectious  lesions  especially,  however,  that 
phlebitis  and  embolism  intervene.  Since  the  researches  of  Cruveil- 
hier  and  Yirchow  their  role  in  the  production  of  pyemia  is  well  known. 
After  having  colonized  in  a  clot,  microbes  manifest  a  stronger  ten- 
dency to  disperse  and  multiply  in  various  organs.  In  fixing  them- 
selves upon  the  vessels  they  seem  to  be  aided  by  solid  particles  which 
serve  them  as  vehicles  of  transportation.  The  secondary  lesions 
which  they  thus  create  are  similar  to  those  of  the  original  focus. 
Such  is  not  always  the  case,  however.  When,  for  instance,  pyogenic 
microbes  derived  from  a  purulent  lesion  make  their  way  into  the 
lung  they  produce  in  the  latter  organ  lesions  which  are  secondarily 
invaded  by  the  bacteria  of  putrefaction,  and  thus  is  formed  a  gan- 
grenous focus. 


336  I27FECTI0  l  's  DISEASES. 

Emboli  generally  follow  a  route1  traced  in  advance  and  governed 
by  the  laws  of  the  circulatory  mechanics.  There  are  exceptional 
cases  described  under  the  name  retrograding  or  paradoxical  emboli. 
Paradoxical  embolism  is  explained  by  the  persistence  of  Botal's 
foramen  (Cohnheim,  Linen.  Zahn).  Retrograde  embolism  is  due  to 
cough  and  effort  which  disturb  the  circulation  in  the  inferior  vena 
cava  and  cause  emboli  to  retrograde  in  the  hepatic  and  even  renal 
veins  (Recklinghausen) . 

Lymphatic  emboli  should  not  be  overlooked,  although  less  impor- 
tant than  blood  emboli.  They  account  for  the  spread  of  microbes, 
and  sometimes,  especially  in  the  thorax,  they  may  be  of  retrograde 
type.  These  emboli  are  interesting  because  they  demonstrate  the 
action  of  the  lymphatic  glands  in  cases  of  visceral  lesions  and  how 
they,  in  their  turn,  may  become  the  source  of  new  lesions. 

The  effect  of  embolism  may  be  immediate  or  remote.  Immediate 
symptoms  are  observed  in  cases  of  large  emboli  arrested  in  the  heart 
or  an  important  vessel.  They  act  mechanically,  give  rise  to  numerous 
and  at  times  very  grave  and  speedily  fatal  disturbances,  due  either 
to  vascular  modifications  or,  more  frequently,  to  influences  of  a 
reflex  order. 

The  violent  dyspnea  and  sudden  death  in  cases  of  voluminous 
pulmonary  emboli  are  due,  I  believe,  to  a  true  inhibitory  action 
aroused  by  the  excitation  of  the  intrapulmonary  terminations  of  the 
pneumogastric  nerve. 

There  are  also  small,  specific  emboli.  Toussaint  attributed  to  them 
an  important  role ;  he  argued  that  most  of  the  symptoms  caused  by 
the  anthrax  bacillus  are  due  to  embolic  obstruction  of  the  capillaries. 
This  view  is  not  acceptable.  The  study  of  infections,  however,  proves 
that  microbes  may  emigrate  through  the  vessels  and  become  fixed 
at  a  certain  point.  When  arrested  the  pathogenic  agent  gives  rise 
to  no  immediate  manifestation;  secondary  lesions,  however,  which 
result  in  the  formation  of  a  new  focus  are  produced  around  it. 
Although  the  process  is  designated  as  microbic  embolism,  there  is 
no  true  embolus:  the  microbes  are  arrested  in  a  vessel  because  its 
walls  are  altered,  and  the  circulation  is  consequently  slow.  Thus,  a 
selective  colonization  takes  place  without  the  sudden  and  abrupt 
arrest  which  characterizes  true  embolism.  Logically,  the  term  in- 
fectious embolus  should  be  employed  when  a  vessel  is  suddenly 
obstructed  by  a  solid  particle  and  notably  by  a  fragment  of  a  clot 
or  valve  impregnated  with  microbes. 


GENERAL  REACTIONS    FEVER. 

Role   of    Modifications  in  the  Organic   Fluids.      The    Vascular     ;. -tern 

may  further  serve  in  the  development  of  secondary  pal  hological  pro- 
cesses by  distributing  throughout  the  organi  m  oluble  products  or 
microbic  toxins  engendered  al  &  certain  point.  It  Is,  however,  like- 
wise owing  to  these  vascular  connections  thai  the  toxins  are  broughl 
to  the  organs  capable  of  transforming  or  eliminating  them.  It  U 
important  to  note  thai  the  increased  work  thut  imposed  upon  the 
glandular  cells  may  give  rise  to  new  lesion  which,  in  their  turn, 
become  the  source  of  other  morbid  proce 

Nervous  Connections.  In  the  presence  of  the  facts  thus  far  con- 
sidered there  can  be  no  escape  from  the  conviction  thai  no  lesion 
can  remain  local.  We  have  not,  however,  yel  taken  into  accounl 
the  highly  importanl  rdle  of  the  nervous  system,  which  constantly 
intervenes  to  establish  solidarity  among  the  various  parts  of  the 
organism.  In  the  course  of  a  disease  the  nervous  system  regulates 
the  formation  of  inflammatory  foci,  produces  vascular  dilatation  or 
constriction,  and  stimulates  or  arrests  liquid  exudations  and  migra- 
tion. It  also  plays  an  important  part  in  the  development  of  certain 
symptoms.  Let  us  take  cough,  for  example.  In  some  respects  this 
is  a  rather  favorable  disturbance,  since  its  effect  is  to  rid  the  respira- 
tory apparatus  of  secretions  obstructing  the  passages.  These  secre- 
tions oppose  the  penetration  of  microbes,  but  their  elimination  by 
coughing  has  the  advantage  of  expelling  the  pathogenic  agents.  In 
order  that  expectoration  may  be  effected  the  synergic  action  of  a 
great  number  of  muscles  is  required.  They  are  excited  to  action 
through  reflex  influences.  The  result  is  the  same,  however,  if  the 
excitant  is  a  poison  or  some  foreign  body.  The  effects  resulting  from 
nervous  connections  possess  nothing  peculiar  in  the  case  of  infection. 
Such  is  also  the  case  when  the  microbe  or  its  toxin  invades  the  organ- 
ism and  becomes  localized  in  the  nervous  system.  The  functional 
modifications  thus  produced  acquire  no  peculiar  character  from  their 
origin.  It  is  necessary  to  remark,  however,  that  intoxication  of  the 
nervous  system  may  give  rise  to  a  great  number  of  functional  dis- 
turbances. In  another  chapter  we  shall  see  that  dyspnea,  cardiac 
disorders,  vomiting,  and  even  anuria  in  many  cases  depend  upon 
intervention  of  the  nervous  system  and  not  upon  a  lesion  of  the 
organs  affected.  In  scarlet  fever,  for  example,  early  anuria  is  seldom 
the  clinical  expression  of  a  renal  lesion :  it  is  due  rather  to  a  nervous 
disorder,  and,  when  the  latter  ceases,  we  are  surprised  to  find  neither 
albumin  nor  casts  in  the  urine. 


338  INFECTIOUS  DISEASES., 


Fever. 


Ft  ver  is  a  morbid  state  resulting  from  the  exaggeration  of  the 
chemical  processes  concerned  in  the  production  of  animal  heat.  These 
chemical  processes  may  be  more  active  and  still  retain  their  normal 
character,  or  they  may  differ  from  those  produced  under  normal 
conditions.  This  distinction  is  of  considerable  importance  from  a 
i  hcrapeutic  standpoint,  but  it  does  not  invalidate  the  definition  above 
given.  Whether  deviated  from  their  habitual  type  or  not  the  chem- 
ical acts  are  more  intense;  this  is  the  characteristic  of  fever. 

The  definition  which  we  propose  explains  the  difference  between 
the  terms  hyperthermia  and  fever.  Hyperthermia  (hyperpyrexia)  is 
rise  of  temperature,  whatever  the  cause.  An  animal  is  placed  in  an 
oven;  its  temperature  rises  1°  or  2°;  we  then  say  that  this  animal 
presents  hyperthermia,  but  there  is  no  question  of  fever.  Hyper- 
thermia none  the  less  constitutes  the  principal  symptom  of  fever. 
Animal  heat  indicates  the  measure  of  the  intensity  of  organic  com- 
bustion under  normal  conditions.  It,  therefore,  also  indicates  the 
changes  which  combustion  undergoes  in  pathological  conditions.  It 
is  intelligible,  however,  that  the  results  may  be  modified  by  increased 
radiation  of  heat.  For  the  sake  of  argument  it  may  be  assumed 
that  increase  in  the  production  of  heat  is  exactly  counterbalanced 
by  increased  radiation.  The  temperature  then  undergoes  no  modi- 
fication. Moreover,  if  radiation  becomes  more  active  it  may  over- 
balance the  production  and,  notwithstanding  the  exaggeration  of  the 
chemical  processes,  the  temperature  falls.  It  is  thus  conceivable  that 
fever  may  be  attended  by  hypothermia. 

These  are  only  theoretical  considerations.  In  order  to  appreciate 
their  value  it  is  necessary  to  complete  the  indications  furnished  by 
the  thermometer  by  means  of  the  calorimeter.  The  amount  of  heat 
lost  is  thus  determined.  Knowing,  on  the  other  hand,  the  modifica- 
tions of  the  temperature,  one  may  easily  calculate  the  quantity  of 
heat  produced.  It  is  precisely  this  quantity  that  measures  the  inten- 
sity of  the  chemical  phenomena.  Fever  may  therefore  be  defined  as 
follows,  which  repeats  in  another  form  the  definition  the  author  has 
given  above :  Fever  is  a  morbid  process  characterized  by  increased 
production  of  animal  heat. 

Unfortunately,  while  thermometry  is  easy  of  application  in  clinical 
medicine,  calorimetry  can  hardly  be  employed  in  current  practice, 
for  it  necessitates  the  use  of  delicate  apparatus  and  disturbs  the 


GENERA  L  REACTIONS— FEVER. 

patient.  According  to  the  results  of  scientific  re  earche  pui  ued  on 
this  matter,  however,  discord  between  calorimetry  and  thermometry 
is  quite  rare  and,  at  all  events,  of  short  duration.  Therefore,  exam- 
ination of  the  temperature  is  generally  sufficient.  Practically,  h  be 
more  important  to  know  the  heal  of  the  body  than  the  radiation  of 
the  calorics,  Tor  it,  is  against  the  modification  in  plus  or  in  minuf  ol 
animal  heat  that  the  physician  has  to  fight.  The  thermometer  alone 
furnishes  him  with  the  necessary  indications. 

Classification  of  Fevers.  All  infections  are  nol  febrile,  nor  are  all 
fevers  infect  ions. 

From  the  standpoint  of  pathological  physiology,  all  fever-  may 
be  divided  into  two  groups:  fevers  of  Qervous  origin  and  fevers  due 
to  intoxication. 

Fevers  of  nervous  origin  may  he  subdivided  into  three  categories: 

First,  algic  fevers  resulting  froi 1 1  painful  excitation.  This  is  besl 
illustrated  by  the  so-called  hepatalgic  fever  observed  in  hepatic  colic-. 
even  when  no  symptom  suggests  infection  of  the  biliary  passages. 
This  fever  has  been  experimentally  produced  in  the  dog  by  means 
of  excitation  of  the  biliary  passages. 

The  fevers  constituting  our  second  group  represent  a  reaction  of 
the  organism  aroused  by  hypothermic  action.  If  an  animal  I  >e  | /laced 
in  a  refrigerator,  especially  if  care  be  taken  to  immobilize  it,  its  tem- 
perature falls.  If  the  animal  then  be  released  and  placed  in  a  warm 
locality,  the  temperature  rises  and  exceeds  the  normal.  The  process 
is  surely  one  of  febrile  character,  for  the  hyperthermia  expresses 
increased  combustion  on  the  part  of  the  animal  in  order  to  struggle 
against  the  excessive  dissipation  of  heat. 

In  the  same  group  may  be  classed  reactionary  fevers  consecutive 
to  toxic  hypothermia.  For  example,  an  individual  has  ingested  car- 
bolic acid;  his  temperature  falls  to  95°  F.  (35°  C);  a  few  hours  later, 
however,  it  rises  and  reaches  102.2°  or  104°  F.  (39°  or  40°  C  . 

The  third  variety  comprises  the  febrile  movements  occasioned  by 
traumatism  affecting  certain  parts  of  the  nervous  centres.  Their 
reality  has  been  demonstrated  by  some  observations,  notably  by  a 
case  of  meningeal  hemorrhage  observed  in  our  wards  and  recorded 
by  Dr.  Josue:  also  by  experimental  researches,  those  of  J.  F.  Guyon 
among  others.     Hysterical  fever  may  also  be  classed  here. 

Fevers  of  toxic  origin  are  by  far  the  most  important.  They  also 
include  three  varieties.  At  times  febrile  movement  is  consecutive 
to  the  introduction  into  the  organism  of  completely  formed  toxic 


340  IXFECTIO  US  DISEASES. 

substances  proceeding  from  without.  The  number  of  hyperthermiz- 
ing  substances  is  quite  restricted.  We  may  cite  strychnine  and 
cocaine.  At  other  times  fever  is  due  to  autointoxication,  and,  finally, 
to  microbic  intoxication. 

The  reality  of  fevers  due  to  autointoxication  has  been  demon- 
strated by  numerous  experiments  and  rigorous  clinical  observations. 
"With  this  group  should  be  classed  the  fever  of  gouty  and  chlorotic 
patients,  the  fever  consecutive  to  the  absorption  of  traumatic  san- 
guineous exudates  and  to  attrition  of  tissues,  certain  forms  of  fever 
due  to  overexertion,  and  the  fever  of  asphyxia, 

The  fevers  of  microbic  origin  evidently  constitute  the  most  impor- 
tant group.  As  has  already  been  stated,  however,  infections  are  not 
always  pyrogenic.  Chronic  diseases,  such  as  syphilis,  may  evolve 
without  being  attended  by  any  elevation  of  temperature.  The  beha- 
vior of  a  given  infection  may  altogether  differ  from  one  individual 
to  another.  Unquestionable  observations  of  apyretic  typhoid  and 
scarlet  fevers  have  been  published.  Apyretic  erysipelas  is  not  of 
uncommon  occurrence.  Habitually  pyrogenic  infections,  such  as 
pneumonia,  are  in  certain  cases  attended  by  subnormal  temperature. 
These  well-known  facts  lead  us  to  the  admission  that  the  role  of  the 
organism  is  vastly  more  important  than  that  of  the  microbe  in  the 
production  of  fever.  We  shall  see  that  this  idea  is  confirmed  by 
numerous  experiments. 

It  must  be  recognized,  however,  that  the  great  majority  of  acute 
and  even  some  chronic  infections  are  accompanied  by  fever  and 
hyperthermia.  Are  the  fever  and  hyperthermia  due  to  microbic 
toxins?  Experimentation  seems  to  answer  affirmatively.  The  injec- 
tion of  sterilized  cultures  into  animals  produces  not  only  hyper- 
thermia, but  true  fever,  with  all  its  modifications  in  chemical  pro- 
cesses. The  problem  is,  however,  more  complex  than  appears  at  first 
sight.  All  substances  capable  of  affecting  the  temperature  produce  a 
primary  action  followed  by  a  secondary  reaction  of  a  reverse  charac- 
ter. In  most  cases  the  latter  is  not  intense ;  it  may,  however,  especially 
in  infections,  be  more  pronounced  than  the  primary  phenomenon 
and  appear  so  rapidly  as  to  completely  mask  the  primary  action. 

The  questions  confronting  us,  therefore,  are:  Does  fever  result 
from  a  microbic  action?  Does  it,  on  the  contrary,  represent  a  reac- 
tion of  the  organism  against  the  action  of  the  microbe  which  tends 
to  produce  hypothermia?  The  latter  conception  seems  to  us  most 
in  harmony  with  experimental  facts. 


GENERAL  REACTIONS    /'/■-  vi.i:.  3  1 1 

Let  us  first  consider  the  primary  element  of  a  greal    number  of 
febrile  processes    i.  r.,  chilU.    At  present  we  know  thai  chills  repre- 
sent a  means  of  getting  warm  when  the  body  is  cold.    Accordii 
the  hypothesis  that  toxins  directly  produce  fever,  It  would  l"'  m 
sary  to  admit  that  they  are  capable  of  directly  stimulating  the  nerve 
(■en  1  res  eoneerneil  in  the  production  of  chills.   This  might  be  possible, 
but  nothing  proves  it ,  and  the  easier  study  of  ordinary  chills  reveals 
no  similar  fact.     II    may  be  objected  that  chills  generally  appear 
when  the  central  temperature  has  already  begun  to  rise.    Thie  result 
simply  proves  that  the  organism  began  to  react  against  the  hypother- 
mizing  action  of  toxins,  but  thai  its  reaction  was  insufficient .  and  for 
that  reason  it  had  recourse  to  chills,  which  represenl  a  rapid  pr< 
of  producing  heat. 

A  febrile  paroxysm  ends  by  profuse  sweating.  From  the  stand- 
point of  thermal  regulation,  perspiration  represents  the  reverse  of 
chills.  It  is  a  means  employed  by  the  organism  for  lowering  its 
temperature.  Now,  if  fever  is  directly  produced  by  microbic  toxins, 
why  does  not  perspiration  appear  sooner?  This  would  materially  aid 
the  organism  to  combal  the  hyperthermizing  action  of  toxins.  If, 
on  the  contrary,  we  admit  that  fever  is  an  expression  of  a  reaction 
on  the  part  of  the  organism,  it  is  readily  conceivable  that  it  is  no 
longer  of  any  use  when  the  action  of  toxins  ceases.  The  sweats  do 
not  appear  from  the  first,  because  the  organism  is  struggling  against 
a  hypothermizing  substance;  as  soon,  however,  as  the  action  of  the 
latter  ceases,  reaction  is  useless  and  perspiration  begins. 

If  microbic  toxins  are  hypothermizing,  why  does  the  temperature 
rise  above  the  normal?  It  would  seem  that  the  organism  should  react 
only  with  energy  sufficient  to  keep  the  bodily  heat  at  its  habitual 
level.  In  reality,  the  reactions  of  the  organism  are  not  always  meas- 
ured to  the  salutary  effect.  They  often  exceed  the  end,  and,  from 
this  point  of  view,  reaction  is,  in  the  present  case,  too  intense.  It 
has  not  been  demonstrated,  however,  that  this  exaggeration  of  the 
process  is  useless. 

Reasoning  thus  leads  us  to  the  assumption  that  fever  is  a  reaction 
of  the  organism.  It  will  now  be  seen  that  experimentation  gives 
considerable  support  to  this  theory. 

Action  of  Microbic  Toxins  upon  Temperature.  Microbic  toxins 
possess  the  property  of  exciting  fever  when  injected  in  small  amounts : 
when  introduced  in  large  doses  they  lower  the  temperature.  The 
experiments  of  Sanarelli  with  the  typhoid  toxin,  those  of  Metchnikoff 


342 


IXFECTIOUS  DISEASES. 


with  tin'  toxin  of  hog-cholera  are,  from  this  point  of  view,  demon- 
strative. The  author  obtained  a  similar  result  with  the  toxin  of  the 
colon  bacillus.  This  toxin  is  said  to  be  hypothermizing;  in  fact,  that 
is  what  occurs  when  large  doses  are  injected.  When,  however,  small 
amounts  are  introduced,  organic  reaction  takes  place  and  the  tem- 
perature rises.  A  glance  at  Fig.  15  will  show  that  a  dose  of  ten  drops 
produces  a  thermal  rise  of  1°  or  1.5°  C,  which  persists  for  five  or  six 
hours. 

A  very  small  dose,  not  exceeding  half  a  drop,  gives  rise  to  a  more 
intense,  at  least  more  rapid,  febrile  movement.    On  the  other  hand, 

Fig.  15. 


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Action  of  the  colon  bacillus  toxin  upon  the  temperature.     I.  Injection  of  0.025  c.cm.  of 
toxin  into  a  vein.    II.  Injection  of  0.5  c.cm.     III.  Injection  of  IS  c.cm. 

large  closes  tend  to  lower  the  temperature — their  first  effect  is  to 
hypothermize ;  the  organism  then  reacts,  and  the  temperature  rises. 
It  remains  close  to  the  normal  and  then  rapidly  falls  at  the  moment 
of  death. 

The  theory  which  I  advocate  likewise  explains  the  differences 
observed  in  the  variations  of  temperature  according  to  the  mode 
of  introduction  of  the  toxin.  If  a  large  dose  is  injected  into  the 
veins  or  the  peritoneum,  absorption  is  rapidly  effected,  and  the 


GENERA  L  BEA<  'TIONS    FEVER. 


343 


temperature  falls  until  the  momenl  of  death.  It  the  same  amount 
is  deposited  in  the  subcutaneous  cellular  ii-  ue  ,  absorption  being 
slower,  the  organism  has  time  to  react;  the  temperature  a1  first 
rises,  to  undergo  a  subsequenl  fall. 

I  have  found  the  same  differences  by  introducing  the  toxin  of  the 
colon  bacillus  by  a  peripheral  vein  and  by  a  branch  of  the  portal 
vein.  In  the  latter  instance  the  poison  passes  through  the  liver, 
which  possesses  the  power  of  arresting  and  neutralizing  a  pari 
of  it.    Two  rabbits  of  nearly  equal  weight  received  each  20  c.cm. 


Fio.  18. 


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Influence  of  the  liver  upon  febrile  reaction.     A.  Injection  of  20  c.cm.  of  toxin  by  the 
portal  vein.     B.  Injection  of  20  c.cm.  of  toxin  by  a  peripheral  vein. 

of  slightly  attenuated  colon  bacillus  toxin.  In  order  to  render 
the  results  comparable,  both  rabbits  were  bound  for  about  half 
an  hour  to  the  experiment  plank,  and  the  one  which  received 
the  poison  by  an  auricular  vein  was  subjected  to  a  laparotomy. 
The  two  animals  were  thus  placed,  with  a  view  to  the  thermal 
reactions,  under  absolutely  identical  conditions.  As  soon  as  the 
animals  were  released  the  temperature  in  both  was  found  lowered 
by  1.5°  C.  From  that  moment  on,  however,  the  temperature  rapidly 
rose  in  the  animal  injected  by  the  portal  vein  (A,  Fig.  16),  and 


344  INFECTIOUS  DISEASES. 

exceeded  the  normal  by  2°  C.  In  the  other  (B,  Fig.  16)  it  first 
continued  to  fall,  then  rose  to  its  initial  figure,  to  again  fall  rapidly 
at  the  moment  of  death.  This  animal  succumbed  at  the  end  of 
seven  hours  and  a  half;  the  other — the  one  which  received  the  toxin 
by  a  branch  of  the  portal  vein — died  only  at  the  end  of  four  days. 

Similar  differences  are  observed  according  as  the  experiment  is 
made  upon  susceptible  or  refractory  animals.  By  inoculating 
anthrax  into  vaccinated  chickens,  dogs,  or  rabbits,  fever  may  be 
produced;  while  in  animals  which  succumb  to  the  infection,  hyper- 
thermia soon  gives  way  to  hypothermia. 

In  the  same  order  of  ideas  may  be  cited  the  experiments  of  Gam- 
aleia,  which  prove  the  thermogenic  action  of  cultures  to  be  in  inverse 
ratio  to  their  virulence.  Thus,  for  example,  the  second  vaccine  of 
anthrax  bacillus,  which  kills  the  rabbit  in  three  days,  first  produces 
a  rise  in  temperature,  reaching  105.8°  F.  (41°  C);  while  an  exalted 
culture  which  kills  the  animal  in  six  or  eight  hours  causes  no  hyper- 
thermia. I  have  reached  a  similar  conclusion  by  employing,  not 
living  cultures,  but  toxins.  Two  cultures  of  the  staphylococcus 
aureus  were  prepared,  one  with  a  specimen  of  moderate  virulence, 
the  other  with  the  same  specimen  considerabty  exalted  by  means 
of  successive  passages.  The  cultures  sterilized  by  means  of  chloro- 
form were  then  injected  into  two  rabbits.  One  of  them  (B,  Fig.  17) 
received  5  c.cm.  of  the  toxin  obtained  from  the  exalted  microbe. 
It  succumbed  at  the  end  of  four  hours  and  a  half  in  hypothermia. 
The  other  (Fig.  17)  received  20  c.cm.  of  the  culture  made  with  the 
attenuated  microbes.  The  temperature  rose  from  103.2°  F.  to 
105.8°  F.  (39.5°  to  41°  C),  and  forty-eight  hours  later  the  animal 
was  still  living.  Its  temperature  then  had  fallen  to  101.1°  F. 
(38.4°  C).  Another  injection  of  20  c.cm.  of  the  same  toxin  was 
given.  This  time  the  temperature  showed  no  modification.  In 
this  organism  already  exhausted  by  a  first  intoxication  reaction  was 
no  longer  possible,  and,  in  fact,  the  animal  was  found  dead  the 
following  morning. 

This  experiment  shows  that  an  animal  weakened  by  a  previous 
injection  is  no  longer  capable  of  developing  fever.  The  result  would 
be  absolutely  incomprehensible  if  fever  was  held  to  be  the  result  of 
the  action  of  the  toxin;  it  becomes  very  clear,  however,  when  it 
is  considered  as  a  reaction  of  the  organism.  This  experimental  fact 
elucidates  certain  clinical  observations.  It  explains  why  cachectic, 
exhausted  individuals  develop  no  fever  on  the  occasion  of  an  infec- 


GENERAL  REACTIONS    /•'/•;  I  I  E 


346 


tion.  [t  likewise  accounts  for  the  fad  thai  an  intercurrenl  infection 
supervening  in  an  individual  already  i i(,k  may  lower  the  temperature 
instead  of  raising  it.  This  is  whal  occurs,  for  example,  in  certain 
cases  of  pneumonia  developing  in  the  course  of  a  typhoid  fever. 
The  organism,  already  saturated  with  the  typhoid  toxin,  if  unable 
bo  struggle  againsl  the  effects  of  a  new  toxin;  therefore,  instead  of 
rising,  as  in  a  healthy  individual,  the  temperature  falls. 

By  another  series  of  experimental  infection-  we  observed  thai 
the  genera]  state  of  the  animals  remains  quite  satisfactory  ae  long 
as  fever  lasts,  and  thai  aggravation  of  the  symptoms  coincides  with 
the  fall  of  temperature. 


Fig. 


lal   Hay 

2d  Dmjr 

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101 

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100.  i° 
98.6° 

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1 

Action  of  staphylococcic  toxin  upon  temperature.  A.  Intravenous  injection  of 
20  c.cni.  of  a  moderately  active  toxin;  a  similar  injection  on  the  third  day.  B.  Intra- 
venous injection  of  5  c.crn.  of  an  active  toxin. 


In  man  the  course  of  temperature  is  in  general  different :  in  the 
great  majority  of  acute  infections  death  supervenes  in  the  midst 
of  hyperthermal  phenomena.  Algid  collapse  is  seldom  observed  at 
the  end  of  diseases.  The  reason  resides  in  the  fact  that  man  suc- 
cumbs before  having  exhausted  all  his  resources:  the  animal  dies 
when  it  is  absolutely  incapable  of  struggling  against  infection,  when 
its  reactionary  power  is  completely  extinct.  Such  is  not  the  ca.se 
with  man,  because  his  more  sensitive  nervous  system  is  sooner 
poisoned.  In  the  animal  the  subordinate  tissues,  the  organs  of 
secondary  importance,  succumb  almost  simultaneously  with  the 


346  ISFECTIO  US  DISEASES. 

nervous  system:  at  The  approach  of  death  general  nutrition  is 
hindered,  chemical  actions  are  on  the  decline,  and  the  temperature 
is  falling;  the  mammalian  is  thus  practically  transformed  into  a 
cold-blooded  animal.  When  a  moribund  animal  is  killed,  red  blood 
is  found  in  its  veins  and  right  heart.  Even  the  tissues  are  found 
modified  in  the  very  same  manner  as  in  animals  artificially  subjected 
to  cold.  The  nervous  system  of  man  cannot  accommodate  itself 
to  the  same  unfavorable  conditions  as  that  of  the  animal.  It  dies 
while  the  other  tissues  are  still  in  full  activity,  and  the  chemical 
actions  still  keep  its  temperature  above  the  normal  level. 

In  certain  instances,  however,  human  infections  lower  the  temper- 
ature. Such  is  the  case  in  cholera  and  choleriform  enteritis.  Such 
is  likewise  the  case  in  very  acute  infections,  in  certain  septicemias 
consecutive  to  major  surgical  operations,  and  the  evolution  of  which 
resembles  that  of  traumatic  shock.  Under  these  conditions  the 
organism  is  rapidly  overwhelmed  and  incapable  of  reacting ;  accord- 
ing to  an  expression  of  Weber,  the  patient  dies  in  chills  and  fever. 

This  result  is  in  perfect  harmony  with  the  experimental  facts 
above  related.  It  demonstrates  that  fever  is  not  produced  except 
when  the  organism  is  still  able  to  react. 

Mechanism  of  Fever.  Let  us  now  inquire  as  to  what  this  reaction 
consists  in:  does  it  reside  in  increased  production  of  heat  or  in  the 
retention  thereof?  Both  hypotheses  have  their  advocates.  Certain 
experiments,  notably  those  of  Rosenthal  and  Maragliano,  demon- 
strate that  during  the  stage  of  initial  rise  the  radiation  of  heat 
diminishes — a  fact  which  is  strictly  in  accord  with  those  above  re- 
ported. At  the  beginning  of  the  febrile  movement,  when  the  central 
temperature  is  already  rising,  the  peripheral  is  below  the  normal; 
it  is  at  that  moment  that  chills  are  called  into  play.  Then  both 
temperatures  rise,  but  not  with  the  same  rapidity,  so  that  the  differ- 
ence between  the  central  and  the  peripheral  temperature  may  at 
times  amount  to  18°  F.  (10°  C).  The  dissipation  of  heat  during 
the  stationary  period  is  equal  to  or  greater  than  the  normal.  In 
cases  of  transitory  febrile  paroxysms  the  dilatation  of  the  cutaneous 
vessels,  which  augments  the  radiation  of  heat,  is  produced  before 
defervescence.  In  cases  of  prolonged  fever  there  is  increased  radia- 
tion throughout  the  stationary  period. 

It  results  from  these  facts  that,  even  if  there  is  a  retention  of 
caloric  at  the  beginning  of  a  febrile  movement,  it  is  exaggerated 
production  that  characterizes  the  stationary  period.      The    losses 


GENERAL  REACTIONS    FEVER.  :;I7 

being  greater,  the  higher  temperature  musl  be  due  to  exaggerated 
production.  Ii  is  to  be  noted,  however,  thai  the  increa  e  in  radia- 
tion of  heal  is  not  proportional  to  the  increase  in  H    production; 

hence  there  is  partial  relent  ion  df  the  heal  produced. 

It  may  now  he  asked  whether  there  i  b  simple  increase  of  the 
normal  chemical  processes  or  a  deviation  from  t  he  physiological  type. 

In  order  to  solve  this  problem,  the  excrementitious  products 
eliminated  by  the  respiratory  or  urinary  apparatus  -hould  be 
analyzed. 

Some  authors,  studying  the  gases  of  respiration,  noted  an  increase 
in  the  exchanges.  WCitheim,  on  the  other  hand,  ie  of  ;i  different 
opinion.  Less  oxygen  is  absorbed,  and  on  this  point  he  is  sup- 
ported by  ITenrijean's  investigations.  The  :iinoimt  of  carbonic  acid 
likewise  undergoes  a  diminution.  The  contrary  result  is  due.  accord- 
ing to  Senator,  to  the  fact  thai  the  elimination  of  this  gas  is  more 
complete  as  a  result  of  the  acceleration  of  the  respiratory  move- 
ments and  diminution  of  the  alkalinity  of  the  blood. 

Dr.  Robin  has  reached  conclusions  which  seem  to  harmonize  the 
dissimilar  results  above  reported.  He  carefully  distinguishes  plain 
inflammatory  infectious  states  from  grave  typhoid  conditions.  In 
the  former  instance  oxidations  are  at  times  normal,  oftener  more 
active;  they  are  diminished  in  the  latter.  This  distinction  elucidates 
not  only  the  modifications  in  the  gaseous  exchanges,  but  also  the 
variations  observed  in  the  composition  of  the  urine.  The  urea  is 
increased,  often  from  50  to  100  per  cent.  (Unruh,  Senator),  in  acute 
cases;  while  in  grave  typhoidal  states  and  in  fevers  of  long  duration 
the  amount  decreases;  the  extractive  matters  are  then  found  to  be 
augmented.  Probably  the  alterations  developing  in  the  cells, 
notably  in  those  of  the  liver,  prevent  the  normal  elaboration  of 
the  products  of  dissimilation.  These  are  produced  in  excess,  a  fact 
which  accounts  for  the  thermal  elevation,  but  are  rejected  before 
having  undergone  their  complete  evolution.  Finally,  the  disturb- 
ances of  the  respiratory  function  seem  to  be  the  main  cause  of  the 
excess  of  uric  acid  so  often  observed  in  the  urine  of  those  suffering 
from  fever  (Ranke). 

Thus  fever  is  due  to  increased  chemical  activity,  whether  or  not 
there  be  concomitant  departure  from  the  normal  evolution  of  matter. 
Dissipation  of  heat  in  fever  is  more  marked  than  under  normal  con- 
ditions, but  excess  in  production  of  heat  is  still  more  marked,  hence 
the  relative  retention  of  caloric  and  rise  in  temperature. 


348  IXFECTIO  US  DISEASES. 

Role  of  the  Blood  in  Thermal  Regulation.  The  first  question  is 
whether  the  blood  is  pyrogenic  in  animals  suffering  from  fever.  In 
this  investigation  the  action  of  normal  blood  upon  the  temperature 
must  previously  be  determined.  The  writer  has  pursued  a  series 
of  very  delicate  experiments  which  are  yet  in  part  unpublished  and 
which  have  led  him  to  some  definite  conclusions  concerning  this 
subject. 

Blood  taken  from  the  carotid  artery  of  a  rabbit  was  injected  into 
the  auricular  vein  of  another  animal  of  the  same  species,  care  being 
taken  to  operate  with  extreme  rapidity,  in  order  to  prevent,  as  far 
as  possible,  the  modifications  which  are  easily  produced  in  blood 
outside  the  vessels.  The  blood  of  a  dog,  taken  under  the  same 
conditions,  was  injected  in  the  same  manner.  The  experiment  was 
also  made  with  defibrinated  blood. 

Two  opposite  results  were  obtained.  There  occurred  a  slight 
diminution  of  temperature  when  total  blood  was  introduced  into 
a  vein,  varying  from  one-tenth  to  four-tenths  of  a  degree  Centigrade. 
There  was  a  marked  rise  of  temperature  when  the  same  blood  was 
injected  defibrinated,  the  hyperthermia  thus  produced  varying  from 
half  a  degree  to  one  degree  Centigrade.  Defibrinated  blood  acts  as 
the  extracts  of  tissues;  in  some  cases,  however,  the  hyperthermia 
which  it  causes  is  preceded  by  a  slight  hypothermia.  The  blood 
serum  acts  like  defibrinated  blood. 

Several  hypotheses  may  be  advanced  to  explain  these  strange 
differences  which  are  observed  according  as  total  or  defibrinated 
blood  is  injected. 

Defibrinated  blood  is  considered  by  many  authors  as  a  fluid  in- 
capable of  serving  for  the  nutrition  of  the  organism.  To  inject  it 
into  the  veins  would  mean  to  introduce  a  toxic  substance,  and  the 
febrile  movement  resulting  would  then  be  intelligible.  Recent 
experiments  of  Dastre  have  demonstrated,  however,  that  defibrin- 
ated blood  is  perfectly  adapted  for  supplying  the  needs  of  the 
economy.  An  animal  may  be  bled,  and  its  defibrinated  blood  may 
again  be  introduced  into  its  circulation  without  any  serious  dis- 
turbance. 

The  marked  instability  of  organic  matter  may  suggest  the  supposi- 
tion that  blood  becomes  thermogenic  simply  because  it  has  been  in 
contact  with  air  or  because  it  has  been  kept  for  a  while  outside  the 
vessels.  With  a  view  to  verify  this  hypothesis  we  received  a  certain 
amount  of  blood  in  a  vase  covered  with  vaseline.     As  Freuncl  has 


GENERAL  REACTIONS    FEVER.  .;i:> 

shown,  under  these  conditions  coagulation  i-  notably  retarded.    At 
the  end  of  half  an  hour  the  Mood,  which  was  perfectly  liquid, 
injected  into  the  veins;  ii   produced  aslighl  hypothermia  like  the 

normal  blood. 

II,  may  be  supposed  thai  the  hypothermizing  power  of  total  blood 
is  due  to  the  presence  of  fibrinogenic  substance]  the  latter,  becoming 
insoluble,  allows  an  antagonistic  substance  to  act.  Thi  hypothesis 
is  also  contradicted  by  fuels.  For  the  production  of  thermal  eleva- 
tion it  suffices  to  injeei  a  liquid  containing  some  fibrinogenic  sub- 
stance, for  example,  the  fluid  of  pleurisy  or  of  hydrocele.  The 
serosity  of  pleurisy  acts,  then,  like  the  bloodserum.  h  firsl  Induces 
a  slight  hypothermia,  and  subsequently  raises  the  temperature. 
Hayein1  likewise  obtained  hyperthermia  by  injecting  hydrocele  fluid 
into  the  veins  of  a  dog. 

What  is  known  of  ferments  is  in  favor  of  the  assumption  thai  the 
thermogenic  action  is  due  to  the  fibrin  ferment.  Several  observers, 
and  notably  Prof.  Hayem,  have  conclusively  shown  thai  this  fermenl 
raises  the  temperature.  Since  its  amount  notably  increases  in 
defibrinated  blood  and  in  serum,  it  was  natural  to  attribute  to  it 
the  thermogenic  property  of  these  fluids.  "When,  however,  defibrin- 
ated blood  is  heated  to  140°  F.  (60°  C.)  sufficiently  long  to  destroy 
the  ferments,  the  thermogenic  power  of  this  fluid  is  by  no  mean- 
abolished.  On  the  other  hand,  the  results  obtained  by  study  of 
the  extracts  of  blood  prepared  by  means  of  alcohol  or  dialysis 
warrant  complete  denial  of  the  influence  of  this  ferment. 

The  nature  of  the  substances  capable  of  modifying  animal  heat 
remains  therefore  undetermined.  The  facts  simply  warrant  the 
conclusion  that  total  blood  is  slightly  hypothermizing.  and  that 
defibrinated  blood  and  serum  raise  the  temperature,  and  sometimes 
raise  it  after  having  first  lowered  it. 

There  exist,  however,  certain  cases  in  which  arterial  total  blood 
is  thermogenic,  for  instance,  when  the  animal  which  furnishes  the 
blood  is  sick  or  when  it  is  submitted  to  the  action  of  cold.  It  is 
not  even  necessary  that  the  central  temperature  be  lowered  in  order 
to  render  the  arterial  blood  thermogenic.  Several  times  animals 
that  had  stayed  outdoors  in  cold  winter  days  furnished  the  blood 
which  raised  the  temperature  of  the  transfused  animals.  It  suffices 
to  keep  the  animal  in  a  well-heated  room  for  twenty-four  hours 
to  cause  the  new  property  to  disappear. 

1  Hayem.     Du  saug.  Paris.  1SS9.  p.  239. 


350  INFECTIO  US  DISEASES. 

Action  of  venous  blood  upon  the  temperature.  A  series  of  ex- 
periments pursued  by  us  demonstrated  that  the  venous  blood,  unlike 
the  arterial,  generally  raises  the  temperature  of  the  animals  into 
which  it  is  injected.  The  hyperthermia  is  variable,  since  at  times 
it  does  not  amount  to  more  than  a  few  tenths  of  a  degree  C,  and 
at  other  times  it  may  attain  1°  C.  or  more. 

As  venous  blood  generally  possesses  a  thermogenic  power  which 
is  absent  from  arterial,  the  question  rises  whether  this  power  depends 
upon  substances  that  are  found  in  the  extracts  of  tissues,  or  whether 
it  is  due  to  bodies  which  appear  in  defibrinated  blood,  serum,  or 
urine.  What  modifications  does  the  blood  undergo  by  passing 
through  the  lungs?  Is  it  a  transformation  or  an  exhalation  of 
volatile  thermogenic  substances  that  occurs?  Such  are  the  ques- 
tions to  be  asked  at  present,  the  solution  of  which  requires  untiring 
experimental  researches. 

Since  arterial  blood  differs  from  venous  by  the  absence  of  a 
thermogenic  substance,  it  is  rational  to  suppose  that  this  substance 
is  eliminated  by  the  lungs.  This  is,  in  fact,  what  takes  place.  The 
water  obtained  by  the  condensation  of  the  expired  air  when  injected 
in  minute  doses  into  the  rabbit  causes  a  more  or  less  marked  rise 
in  the  temperature. 

The  hypothermizing  power  of  arterial  blood  depends  upon  a  sub- 
stance antagonistic  to  that  eliminated  by  the  lungs;  this  substance 
likewise  exists  in  venous  blood,  but  it  is  often  masked  by  the  thermo- 
genic substance. 

The  hypothermizing  substance  proceeds  from  the  tissues  and  is 
eliminated  by  the  kidneys.  It  is  found  in  the  urine,  associated  with 
a  new  thermogenic  substance.  In  fact,  intravenous  injections  of 
the  urine  produce  an  initial  fall  in  the  temperature,  noted  by  Prof. 
Bouchard,  and  give  rise  secondarily  to  a  thermal  elevation.  Surely 
we  are  in  the  presence  of  two  antagonistic  substances,  for  I  have 
succeeded  in  separating  them.  When  the  urine  is  treated  with 
alcohol  the  insoluble  substances  precipitated  in  the  fluid  lower  the 
temperature,  while  the  soluble  ones  raise  it. 

It  is  readily  conceivable  that  these  substances,  concerning  the 
chemical  nature  of  which  we  have  no  data  and  which  we  know  only 
through  their  action  upon  the  organism,  may  normally  play  a  role 
in  the  regulation  of  the  temperature.  Cold,  by  stimulating  the 
renal  secretion,  promotes  the  elimination  of  the  hypothermizing 
substance  and  hinders  the  exhalation  of  the  volatile  thermogenic 


GENERA  L  REACTIONS— FEVER.  :>,:,] 

element.  The  effect  of  heal  is  evidently  the  reverse  of  this;  il 
stimulates  the  elimination  of  the  volatile  thermogenic  substance, 
diminishes  the  secretion  bythe  kidneys,  and  binder*  the  elimination 
of  the  hypothermizing  element . 

These  data  may  explain  certain  pathological  facte  and  notably 
the  hyperthermia  produced  by  asphyxia  and  the  thermal  variation* 
in  cases  of  uremia.  As  we  shall  see,  they  elucidate  a  certain  number 
of  features  in  the  study  of  infectious  fevers. 

Role  of  the  Liver,  Kidneys,  and  Lungs  in  Thermogenesis.  Feb- 
rile movemenl  may  be  profoundly  modified  by  lesions  or  disorders 
of  certain  organs.  As  yet  the  influence  of  the  liver,  kidneys,  and 
lungs  only  is  known. 

My  attention  was  drawn  to  the  r61e  of  the  liver  by  observation  of 
two  cases  of  typhoid  fever  at  the  end  of  ls(M).  The  Btrange  course  of 
the  temperature  could  be  accounted  for  only  by  the  far-reaching 
alterations  which  the  necropsy  revealed  in  the  liver.  The  distur- 
bances were  so  pronounced,  and  modified  the  clinical  course  of  events 
to  such  a  degree,  that  the  author  thought  a  hepatic  type  of  typhoid 
fever  should  be  admitted.  Setting  aside  the  concomitant  symptoms, 
let  us  consider  only  the  course  of  the  temperature.  The  temperature, 
lowered  in  both  cases,  returned  to  the  normal,  and  fell  even  below 
98.6°  F.  (37°  C).  Coincidently  the  general  phenomena  became  aggra- 
vated, and  the  patient  succumbed  at  a  time  when,  if  the  febrile 
tracing  only  was  taken  into  consideration,  it  would  have  been  thought 
that  he  was  recovering.  The  autopsy  revealed  complete  degenera- 
tion of  the  liver,  with  a  bloodless,  yellow  parenchyma.  It  was  hyper- 
trophied  and  weighed  1930  grams  in  one  case.  2630  in  the  other 
(normal  weight  being  1500  grams).  Histological  examination  ami 
chemical  analysis  showed  that  the  gland  had  undergone  acute  fatty 
degeneration;  the  amount  of  fat.  which  normally  is  about  2  per  cent., 
exceeded  9  per  cent. 

It  seemed  to  me  rational  to  connect  the  unusual  course  of  the  fever 
with  the  hepatic  alteration.  In  order  to  verify  this  supposition  the 
author  undertook  some  experimental  researches.  The  ideal  would 
evidently  be  to  study  the  course  of  the  temperature  in  animals  whose 
liver  had  been  extirpated.  Such  mutilation,  however,  is  not  com- 
patible with  a  survival  sufficiently  long  to  yield  demonstrative 
results.  Some  other  method  should  therefore  be  employed.  The 
researches  of  Denys  and  Strubbe  and  those  pursued  by  the  author 
with  Dr.  Gouget  demonstrate  that  it  is  possible  to  destroy  the  hepatic 


352 


ISFECTIO  US  DISEASES. 


cells  or.  at  least,  the  greater  part  of  them,  by  injecting  a  dilute 
solution  of  acetic  acid  into  the  biliary  passages. 

The  operation  is  quite  simple.  A  fine  canula  is  introduced 
through  the  duodenum  into  the  ductus  choledochus  in  such  a  manner 
as  not  to  disturb  the  course  of  the  bile.  The  experiment  lasts  for 
about  half  an  hour,  and  the  immobilization  of  the  animal  and  the 
reflex  disturbances  resulting  from  section  of  the  abdomen  lower  the 
temperature. 

It  was  therefore  necessary  to  previously  study  the  hypothermia 
induced  by  laparotomy.     We  learned  that  it  generally  oscillates 

Fig.  IS. 


1 1 

(Ol»       12   1    IS 

21 

80 

3G       42 

43 

54 

GO 

GG 

72 

102.2° 

100.4C 

98.G° 

8D.8C 

95° 

~93.2= 

< 91.4° 

|  S9.6C 

t-            0 

87.8" 

86° 

81.2" 

S2.4" 

80.6" 

78.8' 

, 

| 

\ 

y 

\ 
\ 

\ 
\ 

\ 

\ 

I 
1 

\ 

: 

' 

\ 
\ 

E: 

cp.I 

\ 

ixp. 

ill 

Ex] 

Kill 

Course  of  temperature  in  animals  in  which  the  liver  was  extirpated. 


about  2.7°  F.  (1.5°  C.)  and  lasts  for  a  short  time;  as  soon  as  the 
animal  is  released  the  temperature  again  rises.  If,  on  the  contrary, 
the  hepatic  gland  is  subjected  to  injury,  the  temperature,  which  at 
times  first  rises,  soon  undergoes  a  new  fall  in  a  definite  manner,  after 
having  often  presented  slight  and  transitory  rises.  Thus,  in  a  rabbit 
in  which  5  c.cm.  of  a  2  per  cent,  dilution  of  acetic  acid  had  been 
injected  into  the  biliary  passages,  the  temperature,  which  was  pri- 
marily at  102.4°  F.  (39.1°  C),  fell  after  the  operation  to  99°  F. 


GENERAL  REACTIONS    FEVER 

(37.4°  C);  it  then  rose  and  two  hours  later  reached  101.1°]     ■:-  I  I 
but  from  that  moment  on  it  declined;  seven  houn  later  ii  wa 
97.9°  F.  (36.6°  C),  and  at  the  end  of  fifteen  hours,  thirty  minute* 
before  death,  it  had  fallen  to  87.8°  F.  (31°  C). 

In  another  rabbit  submitted  to  the  same  experimenl  the  temp 
I, urc  followed  a  similar  movemenl  (Exp.  I,  Fig.  L8). 

When  the  animal  survives  longer  the  phenomena  are  more  inter- 
esting.   Thus,  in  one  rabbil  (Exp.  [I.)  the  temperature  fell  gradually 
to  S4.2°  F.  (29°  C.)  and,  ;i  lew  minutes  before  death,  to  81.5    I 
(27.5°  C). 

In  another  instance  (\')\\).  III.)  the  animal  survived  seventy-two 
hours,  and  the  final  temperature,  a  few  minutes  before  death, 
78.8°  F.  (26°  C). 

These  absolutely  concordant  experiments  prove  that  the  destruc- 
tion of  the  liver  is  followed  by  a  progressive  and  very  marked 
lowering  of  the  temperature.  The  phenomenon  is  quite  difficult  of 
interpretation.  Can  the  liver,  according  to  the.  experiments  of  CI. 
Bernard,  d'Arsonval,  and  Charrin,  be  considered  as  the  main  source  of 
organic  heat?  Can  it  be  assumed  that  destruction  of  this  gland,  by 
suppressing  a  focus  of.  heat,  produces  hypothermia  in  norma]  sub- 
jects and  in  infected  subjects  hinders  the  thermal  rise  which  charac- 
terizes fever?  This  conception  might  be  maintained.  It  seems,  how- 
ever, more  rational  to  assume  that  the  action  of  the  liver  is  an  indirect 
one.  Suppression  of  the  functions  of  this  organ  produces  a  modifi- 
cation in  general  metabolism  of  the  economy,  a  disturbance  of  the 
nutritive  exchanges  which,  under  normal  as  well  as  under  di-  s 
conditions,  represent  the  true  source  of  animal  heat. 

At  all  events,  the  explanation  is  of  less  importance  than  the  fact. 
The  author's  experiments,  by  demonstrating  the  existence  of  a  hypo- 
thermia of  hepatic  origin,  seem  to  elucidate  some  clinical  observa- 
tions. They  account  for  certain  disturbances  observed  in  the  course 
of  infections  affecting  especially  the  liver,  notably  icterus  gravis. 
Apyrexia  and  hypothermia  are  not  rare  in  certain  forms  of  this 
disease.  Is  this  due,  as  Hanot  asserted,  to  the  nature  of  the  infec- 
tious agent  concerned?  AYe  have  experimental  evidence  that  the 
hypothermizing  role  of  the  colon  bacillus  has  been  exaggerated.  Far 
from  lowering  the  temperature,  this  microbe  often  gives  rise  to  fever. 
The  hypothermia  of  icterus  gravis,  therefore,  seems  to  be  due  to 
hepatic  incompetency.  It  is  true  that,  in  certain  cases,  fever  occurs 
in  spite  of  the  hepatic  degeneration,  because  hepatic  insufficiency 

23 


354  ISFECTIO  US  DISEASES. 

does  not  suppress  the  production  of  heat  any  more  than  renal  insuf- 
ficiency does  ;  it  only  diminishes  it.  Moreover,  the  author  has  learned 
by  a  series  of  experiments  that  the  injection  of  microbic  toxins  into 
animals  the  livers  of  which  had  previously  been  destroyed  by  inject- 
ing a  2  per  cent,  dilution  of  acetic  acid  was  followed  by  a  thermal 
elevation  which  caused  the  temperature  to  rise  for  a  moment  to  its 
initial  height. 

The  kidneys  very  likely  play  a  similar  part.  Incompetency  of 
these  organs  likewise  induces  hypothermia,  as  is  evidenced  by  the 
course  of  the  temperature  in  uremic  patients.  It  may,  therefore,  be 
supposed  that  in  a  certain  number  of  infections  fever  undergoes 
oscillations  referable  to  lesions  of  the  kidneys. 

On  the  other  hand,  pulmonary  alterations  represent  an  important 
cause  of  hypothermia,  Few  diseases  give  rise  to  such  high  tempera- 
tures as  pneumonia.  It  may  be  alleged  that  the  phenomenon  is  clue 
to  the  action  of  the  pneumococcus;  it  is,  however,  the  same  with 
bronchopneumonia,  regardless  of  the  pathogenic  agent,  provided,  of 
course,  that  the  sufferer  is  capable  of  reacting,  for  bronchopneumonia 
in  debilitated  persons  is  at  times  attended  by  a  low  temperature 
which  is  fairly  explained  by  the  general  state.  On  the  other  hand, 
that  particular  clinical  form  so  frequent  among  children,  and  which 
was  once  described  as  acute  pulmonary  congestion,  is  at  present 
looked  upon  as  an  abortive  pneumonia  and  is  often  accompanied  by 
high  fever.  Experimentation,  by  demonstrating  that  the  lungs  elim- 
inate thermogenic  substances,  explains  perfectly  their  role  in  the 
development  of  febrile  movements. 

Except  the  nervous  system,  the  influence  of  other  parts  of  the 
organism  is  not  as  yet  known.  Since  the  nervous  system  plays  an 
important  part  in  thermal  regulation,  it  is  readily  conceivable  that 
according  as  the  nervous  centres  are  excited  or  paralyzed  they  may 
increase  or  diminish  the  thermal  degree.  The  intensity  of  fever  in 
children  and  its  absence  in  the  aged  proves  this  assertion. 

To  sum  up:  the  fever  of  infectious  diseases  is  a  reaction  of  the 
organism  against  microbic  toxins.  With  the  same  quantity  of  the 
same  toxin  the  febrile  movement  varies,  on  the  one  hand,  according 
to  the  localization  of  the  process,  and,  on  the  other,  according  to  the 
state  of  the  nervous  system,  and  of  the  blood,  and  of  certain  organs, 
such  as  the  liver,  kidneys,  lungs,  and,  probably,  the  muscular  system, 
since  we  know  that  the  principal  chemical  modifications  calculated 
to  maintain  the  animal  heat  occur  normally  in  the  muscles. 


0  ENER .  I  L  R  /:.  I  ( "/'/ 0  N8    FE  I ' EB, 

[f  the  author's  conception  is  correct,  fever  mu  I  I"-  con  idered  a 
struggle  against  infection.  The  author  speaks  of  fever,  ool  byper- 
fchermia. 

To  return  to  his  definition  of  fever,  the  author  think?-  that  it  i- 
essentially  characterized  by  an  exaggeration  of  the  chemical  pro- 
cesses occurring  in  the  organism.  Whether  there  be  deviation  from 
tin*  normal  type  or  not,  there  is  increase  in  the  phenomena  which 
explain  animal  heat.  In  other  words,  there  i-  increased  activil 
nutrition.  The  organism,  in  order  to  combal  the  hypothermizing 
action  of  toxins,  stimulates  combustion,  and  ae  aoon  ae  a  rise  in 
temperature  occurs  an  exaggerated  dissipation  of  beal  follows. 
This  fact  is  interesting,  since  it  is  an  example — we  shall  Bee  many 
others — of  a  modification  which  indicates  the  reappearance  of  a 
functional  state  characteristic  of  a  younger  age.  Ii  ifl  known 
that  nutrition  as  well  as  radiation  of  heal  diminishes  with  the 
advance  of  age;  fever,  then,  is  a  return  to  a  previous  state  of  the 
organism. 

While  fever  is  useful,  hyperthermia  may  prove  dangerous.  In 
combating  it,  preference  should  be  given  to  those  methods  which 
favor  the  dissipation  of  heat,  while  those  that  hinder  nutritive  activ- 
ity should  be  avoided.  Cold  baths  offer  the  best  method,  since 
under  their  influence  heat  is  readily  dissipated  at  an  increased  rate, 
and  nutrition  is  at  the  same  time  stimulated.  This  method  may. 
therefore,  be  considered  as  a  natural  one;  it  is  suggested  by  the  pro- 
cedure utilized  by  the  organism  itself. 

It  is  not  the  elevation  of  temperature  that  is  to  be  combated,  but 
an  exaggerated  elevation  of  it,  since  a  moderate  hyperthermia  seems 
to  be  favorable  to  the  struggle  against  the  microbes:  it  stimulates 
the  activity  of  the  leucocytes,  as  was  shown  by  Dr.  Maurel,  and  it 
increases  the  germicidal  power  of  the  blood,  as  has  been  demon- 
strated by  Kast,  Henrijean,  and  Rovighi. 

Thus,  in  spite  of  a  few  obscure  points,  we  may  at  the  present  day 
offer  a  rational  conception  of  fever.  In  the  study  of  the  mechanism 
presiding  over  its  development  we  find  valuable  indications  as  to  its 
significance,  its  r61e  in  the  defense  of  the  organism,  its  usefulness  and 
dangers,  and  as  to  the  means  which,  in  certain  cases,  may  be  em- 
ployed for  restraining  and  combating  it. 

Characters  of  Fever  in  Some  Infections.  The  application  of 
thermometry  to  clinical  practice  has  made  it  possible  to  learn  with 
precision  the  characters  of  fever  in  various  infections.     Thus  febrile 


35G 


INFECTIOUS  DISEASES. 


processes  have  been  divided  into  four  classes,  according  as  they  are 
continuous,  remittent,  intermittent,  or  irregular. 

The  continuous  type  is  represented  by  cases  in  which  the  tempera- 
t  ure,  at  the  stationary  periods,  remains  at  a  determined  height.  The 
classical  example  is  typhoid  fever.  It  is  necessary  to  note,  however, 
that  the  temperature  undergoes  daily  oscillations  which  are  even 
more  pronounced  than  under  normal  conditions.  It  is  known  that 
in  health  the  temperature  varies  at  different  hours  of  the  day.  On 
awakening,  at  6  a.m.,  it  is,  on  an  average,  at  98.5°  F.  (36.9°  C); 
it  progressively  rises  for  sixteen  hours,  and  reaches  its  maximum, 
which  varies  from  99.1°  F.  to  99.5°  F.  (37.3°  C.  to  37.5°  C),  toward 
7  p.m.  ;  it  then  declines  for  eight  hours,  until  3  or  4  a.m.,  when  it 
falls  to  98.2°  F.  (36.7°  C),  to  rise  again.     It  may,  therefore,  be  stated 


Fi 

5.   19. 

0 

99.68° 

99.50° 

^  99.32" 

/ 

/ 

\ 

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/ 

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< 

-it  08.50° 

s  98.78° 

H  98.60° 

1 

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7 

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HI 

11 

12 

i 

HOUR  (MORNING)  (EVENING) 

Daily  course  of  the  rectal  temperature  under  normal  conditions  (after  Jurgensen). 

that,  on  an  average,  the  normal  variation  of  temperature  amounts 
to  1.4°  F.  (0.8°  C).  The  same  variations  are  encountered  in  disease, 
but  generally  they  are  more  marked.  In  typhoid  fever  the  morning 
temperature  generally  varies  from  103.1°  to  104°  F.  (39.5°  to  40°  C.) ; 
that  of  the  evening  from  104°  to  105.8°  F.  (40°  to  41°  C.) ;  the  dif- 
ference is  0.9°  to  2.7°  F.  (0.5°  to  1.5°  C). 

The  same  is  true  of  pneumonia  and  typhus,  which  are  likewise 
characterized  at  their  stationary  period  by  a  so-called  continuous 
fever.  The  digressions  are,  however,  no  less  clear  than  in  typhoid 
fever.  It  may,  therefore,  be  stated  that  thermal  variations  in 
diseases  are  generally  nothing  else  than  exaggeration  of  normal 
phenomena. 

When  thermal  remittences  are  considerable  the  temperature 
returns  at  certain  moments  to  the  normal.     The  fever  is  then  said 


QENEBA  L  REACTIONS    FEVER, 


to  If  intermittent     [ntermittenl    fever    are  often  divided  into  two 
groups:  malarial  intermittenl  and  symptomatic  intermittent  f< 

The  regularity  of  malarial  intermil  tence  is  well  known.  The  ymp- 
tomatic  intermittent  fevers  differ  from  the  malarial  in  thai  thej 
less  regular.  Unlike  whal  occurs  in  malaria,  fever  generally  ap] 
in  the  evening,  sometimes  recurs  several  I  imes  in  one  day,  and  reap- 
pears at  different  hours  on  the  following  day.  The  paro  hich 
in  most  cases  arc  related  io  suppurating  loci,  are  connected  with  'lie 
progressively  increasing  lesions:  they  are  intermittent,  while  the  evo- 
lution of  the  lesions  in  continuous.  They  then  resull  probably  from 
a  sudden  reaction  against  ;i  cumulative  ad  ion.  Whatever  the  expla- 
nation may  be,  febrile  intermittence  is  only  an  exaggeration  of 
physiological  remittences. 

I  i.;.  20. 


1 

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M  E 

3 

M  E 

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M  E 

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M  E  1  M  E 

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ME[me[me'me'mE    ME    ME' me 

is  |  in  |  17 

18  |   19      -Jii      Jl      CI 
ME    WE     VE    ME    «E 

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V  \  /\ 

/  \ 

17  \  A  A 

w   \  /  \  /  \    • 

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l    1 

i 

Schematic  tracing  of  temperature  of  a  typhoid  case,  according  to  Wunderlich. 


In  certain  infections  the  course  of  the  temperature  is  so  regular 
that  its  study  aids  diagnosis.  Typhoid  fever  is  the  type  of  this  kind. 
Since  the  works  of  Wunderlich,  the  cyclic  evolution  of  the  tempera- 
ture, with  its  progressive  ascension,  double  summit,  and  descent  by 
lysis,  is  well  known.  (Fig.  20.)  To  this  is  contrasted  the  by  no  means 
less  typical  evolution  of  pneumonic  fever,  with  its  abrupt  onset,  its 
plateau,  and  its  defervescence  by  crisis.  The  value  of  these  characters 
should  not,  however,  be  exaggerated.  Often,  especially  during  grave 
epidemics,  the  course  of  fever  in  typhoid  is  absolutely  atypical.  In 
order  to  be  convinced  of  this  it  will  suffice  to  bear  in  mind  the  course 
of  the  temperature  in  the  hepatic  form  of  the  disease.  Even  in  cases 
with  a  typical  evolution,  however,  the  course  often  deviates  from  the 
schematic  type.  At  times  the  onset,  at  other  times  the  defervescence. 
is    abrupt;    in  other  cases  the  stationary  period  is  remarkable  for 


358  IXFECTIO  US  DISEASES. 

its  oscillations,  its  sudden  falls  and  unforeseen  rises.  On  the  other 
hand,  pneumonia  may  be  attended  by  irregular  fever  and  slow  defer- 
vescence. 

Semiological  Value  of  Thermal  Course.  As  a  result  of  the  admir- 
able contributions  of  Wunderlich  it  was  believed  that  the  deter- 
mination of  the  thermal  traces  would  be  of  great  semiological  value 
and  furnish  important  elements  in  diagnosis.  As  we  have  already 
stated,  a  different  conclusion  is  at  present  reached.  Medical  ther- 
mometry serves  for  differentiating  infections  only  in  exceptional 
instances.  It  serves  rather  to  inform  the  physician  of  the  evolution 
of  the  process,  the  development,  and  at  times  the  imminence  of 
complications,  at  the  same  time  furnishing  him  with  indications  indis- 
pensable for  treatment.  The  unexpected  rises  or  falls  of  the  tem- 
perature lead  him  immediately  to  look  for  the  causes  of  these  unusual 
modifications.  The  changes  of  temperature  may  thus  keep  the 
physician  awake  to  the  occurrence  of  various  incidents,  such  as  an 
intestinal  perforation,  a  hemorrhage,  or  even  a  secondary  infection; 
a  decrease  in  fever  has  on  several  occasions  been  observed  at  a 
moment  when  a  second  pyrogenic  infection  like  pneumonia  devel- 
oped. 

Likewise,  after  an  apparent  recovery  from  sjnnptoms,  the  ther- 
mometer may  inform  us  as  to  a  relapse  or  some  incident  of  convales- 
cence. In  other  instances  it  indicates  that  the  food  given  is  too  rich 
or  too  abundant  or  that  the  slight  exertion  permitted  is  as  yet  too 
fatiguing.  Thus,  while  in  the  course  of  disease  the  thermometer  in 
a  large  measure  guides  the  treatment,  it  directs  hygienic  surveillance 
during  convalescence.  In  both  cases  it  furnishes  valuable  indications 
which  no  other  procedure  can. 


CHA  PTEB    XIII. 

INFLUENCE  OF  [NFECTIONS  UPON  VARIOUS  PARTS  01 

Til K  ullC.WISM. 

Modifications  <>r  the  Blood  in  the  Course  "i  Principal  [nfections.     Modification    in  the 
Physical  and  Chemical  Characters.     Microscopic  Study  of  the  Blood.     Varial 
of  the  Leucocytes  in  i  lie  Principal  Infections.    Bacteriological  Examination.    Modi- 
fications in  the  I  lematopoiet  ic  Organs.     'I'lic   Bone-maiTOW.      i'nliniinar 
of   Normal    Anatomy   ami    Physiology.      Influence   of    Experimental    [nfecl 
Anatomical  and  Chemical  Modifications.     Eieaction  of  the  Bone-marrow  in 
Semiology  of  the  Hone-marrow.     The  Spleen  in   [nfections.     Modifications  in  the 
Lymphatic  Glands.    Variolar,  Syphilitic,  and  Tubercular  Adenopathies.     Humoral 
Modifications  of  Lymphatic  Origin.     The  Thymus  in   [nfections.     The  Thyroid 
Gland  in  Infections.     The  Suprarenal  Capsules  in   infections. 

Modifications  of  the  Blood  in  the  Course  of  Principal  Infections. 

The  diffusion  of  toxins  secreted  by  pathogenic  agents  and  the  inti- 
mate solidarity  uniting  the  different  parts  of  the  organism  sufficient  ly 
explain  the  occurrence  of  more  or  less  marked  modifications  in  the 
organs,  tissues,  and  fluids  under  the  influence  of  infections.  T 
modifications  are  of  two  orders:  some  represent  true  lesions;  others, 
simple  functional  changes.  Of  the  latter,  some  express  an  increase 
in  activity;  at  times  a  return  to  a  previous  state — i.  e.,  a  kind  of 
rejuvenation  of  the  organism.  From  this  standpoint  nothing  is  more 
instructive  than  the  study  of  the  blood  and  of  the  hematopoietic 
organs. 

Examination  of  the  blood  in  the  course  of  infectious  disei  -  - 
enables  us  to  watch  certain  changes  occurring  in  the  activity  of  the 
organs  or  in  the  nutritional  processes  of  the  economy,  and  thus  to 
witness  the  various  phases  of  the  struggle  engaged  between  the  in- 
vading organism  and  the  invaded.  Hematology  has  this  important 
advantage  over  pathological  anatomy  that  it  is  practised  upon  the 
living.  Post-mortem  examination  of  the  viscera  shows  the  results 
of  the  defeat,  but  it  does  not  explain  its  mechanism.  By  enabling 
us  to  determine  at  each  moment  the  conditions  of  the  pathological 
combat,  the  study  of  the  blood  furnishes  us  with  diagnostic  and  prog- 


3G0  IXFECTIOUS  DISEASES. 

nostic  data  of  importance',  and  may  even  suggest  valuable  thera- 
peutic ideas. 
Modifications  in  the  Physical  Characters.    Ancient  physicians, 

who  frequently  resorted  to  bloodletting,  were  able  to  note  the  organo- 
leptic characters  of  the  blood  in  the  course  of  infections,  and  they 
have  left  us  highly  interesting  information  as  to  the  mode  of  coagu- 
lation and  the  appearance  of  clots. 

The  color  of  the  blood  is  generally  darker  than  under  normal  con- 
ditions. This  excessive  venous  character  is  mainly  observed  when 
there  is  a  disturbance  in  hematosis.  Gubler  and  Renaut  have  noticed 
however,  that  in  grave  typhoid  conditions,  malignant  diphtheria,  and 
hemorrhagic  types  of  eruptive  fevers  the  blood  presents  a  violet  hue, 
different  from  the  dark  color  observed  in  asphyxia.  They  attribute 
this  state  to  an  alteration  in  the  hemoglobin.  The  same  appearance 
is  evidently  found  at  the  necropsy.  In  cholera  the  blood  is  remark- 
able for  its  thick  consistence  and  dark  color.  That  this  is  due  to 
some  modification  in  the  hemoglobin  is  demonstrated  by  the  fact 
that  when  shaken  with  oxygen  the  blood  does  not  resume  its  red 
color. 

If  infection  has  lasted  for  a  long  period  and  given  rise  to  anemia, 
the  blood  is  pale  and  rose-colored.  In  some  grave  infections,  par- 
ticularly in  nervous  forms  of  typhus  and  typhoid  fevers,  it  preserves 
an  abnormal  arterialization  in  the  veins;  it  is  reddish  in  color.  This 
may  be  due  to  the  excessive  acceleration  of  the  movements  of  the 
heart  which,  at  a  given  time,  causes  too  much  blood  to  pass  into  the 
tissues,  or  it  may  depend  upon  insufficiency  of  organic  exchanges, 
owing  to  nervous  derangement,  and  expressed  in  a  diminished  pro- 
duction of  carbonic  acid. 

The  blood  commonly  preserves  its  habitual  odor.  In  certain  cases 
of  intense  gastrointestinal  disorders  and  putrid  lesions,  however,  it 
may  be  charged  with  nauseous  gases.  Morton  reports  that  in  a  bad 
case  of  fever  the  fetid  character  of  the  blood  where  it  issued  from  the 
vein  was  such  as  to  almost  cause  the  surgeon  and  his  assistants  to 
faint.  It  is  also  said  that  the  blood  of  variola  and  typhoid  patients 
exhales  a  fetid  odor. 

The  modifications  in  the  consistence  of  the  blood  played,  as  is 
known,  an  important  role  in  the  pathogenic  doctrines  of  Boerhaave. 
It  seems  that  the  blood  is  simply  thicker  as  a  result  of  profuse  loss 
of  fluids,  markedly  in  cholera.  The  total  mass  is  said  to  be  then 
diminished  by  one  kilogram  (quart). 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      36] 

The  mode  of  coagulation  of  the  blood  has  attracted  special  atten- 
tion.    In  some  instances  the  clo!  is  firm,   lightly  retractile,  and 
crcd  with  a  thick,  fibrinous  layer:  this  is  the  blood  of  phlegma 
such  as  is  observed  in  pneumonia,  acute  articular  rheumatism,  and 
certain  phlegmons,     [n  other  cases  the  clot  is  soft,  tending  to  di 
in  the  scrim i :  such  is  the  blood  in  grave  fever-,  i yphua  fever,  bubonic 
plague,  and  typhoid  fever. 

In  plain  phlegmasias,  notably  in  pneumonia,  the  blood  coagulates 
more  slowly  than  under  normal  conditions.  The  clol  is  remarkably 
small,  concentrated,  and  firm;  the  deeper  layers  are  red:  the  outer 
surface  is  formed  of  a  yellowish-white  layer  which  is  firm  and  thick. 
This  appearance  of  the  clol  is  due  to  the  excess  of  fibrin,  the  amounl 
of  which  may  rise  from  2.5  to  10  per  1000.  As  is  known,  fibrin  plays 
an  important  role1  in  the  defense  of  the  organism  againsl  the  pneu- 
moeoccus,  and  it  is  therefore  possible  to  draw  some  valuable  deduc- 
tions with  reference  to  prognosis.  The  upper  layer  is  thicker  in  pro- 
portion as  the  individual  is  more  robusl  and  the  inflammation  more 
intense.  According  to  Hourmann  and  Dechambre,  the  blood  in  the 
aged  is  seldom  covered  by  the  usual  upper  layer,  a  fact  well  in  har- 
mony with  the  lack  of  defensive  reactions  at  this  age.  Louis  and 
Grisolle  have  noted  that,  the  upper  layer  is  often  absent  in  fatal  cases 
and  seldom  lacking  in  favorable  cases  of  pneumonia.  Among  the 
former  it  is  wanting  in  one-fifth  of  the  cases;  among  the  latter  in 
only  one  out  of  eleven  instances.1 

In  grave  pyrexias,  hemorrhagic  types  of  eruptive  fevers,  typhus 
fever,  bubonic  plague,  diphtheria,  and  pneumonia  of  typhoid  form 
the  blood  coagulates  slowly  and  incompletely.  The  clot  is  soft, 
non-retractile.  The  upper  surface  is  plain,  not  concave,  and  covered 
by  a  slight  layer  of  fibrin.  The  serum  is  scanty  and  the  clot  has  a 
tendency  to  dissolve  in  the  serum. 

The  mechanism  of  these  phenomena  has  been  a  subject  of  dis- 
cussion. Some  authorities  have  attributed  them  to  modification 
in  the  amount  of  fibrin,  and  others  to  a  change  in  coagulability  of 
the  latter.  However  this  may  be,  the  amount  of  fibrin  which 
coagulates  varies  markedly  with  the  group  of  infections  considered. 
The  following  figures,  borrowed  from  the  highly  interesting  investiga- 
tions of  Andral  and  Gavarret.  give  a  clear  idea  in  this  respect. 
These  authors  take  the  normal  proportion  of  fibrin  to  be  3: 1000. 

1  Grisolle.     Traite  tie  la  pneumonie.     Second  edition.  1S64.  p.  257. 


3G2  INFECTIOUS  DISEASES. 

X umber  X umber  of  Average 

Disease.                 of  Cases.  Venesection,  of  Fibrin.   Maximum.    Minimum. 

Pneumonia 20  57  7.47  10.5  4.0 

Acute  articular  rheumatism  .    14  41  6.S9  10.2  4.1 

Acute  peritonitis    ....     4  6  6.2                7.2  4.7 

Erysipelas 5  S  5.67               7.3  6.2 

Scarlatina 2  2  3.3                3.5  3.1 

Variola 5  12  2.92                 4.4  1.1 

Measles 7  9  2.S                 3.6  2.4 

Typhoid  fever 19  43  2.52                3.8  0.9 

Spectroscopic  examination  of  the  blood  may  also  be  of  great 
service  for  the  study  of  its  physical  properties,  as  has  been  shown 
by  Henocque.  The  investigations  of  Henocque  and  Beaudoin  prove 
that,  in  typhoid  fever,  the  energy  of  consumption  of  the  oxygen 
of  the  blood  by  the  tissues  is  in  inverse  ratio  to  the  elevation  of 
temperature.  Fever  diminishes  the  activity  of  oxidations  and 
exchanges. 

Chemical  Modifications.  The  chemical  modifications  suffered  by 
the  blood  in  the  course  of  infections  are  extremely  profound,  as  is 
evidenced  by  the  modifications  in  the  biological  properties  of  this 
fluid.  They  are  so  delicate,  however,  and  bear  upon  such  unstable 
substances  that  an  exact  analysis  is  a  matter  of  great  difficulty.  In 
fact,  no  well-marked  changes  are  discovered  when  the  usual  pro- 
cedures are  employed. 

The  reaction  remains  alkaline.  In  some  cases  of  cholera  it  has 
been  found  to  be  neutral  or  slightly  acid.  The  amount  of  water 
varies  inversely  to  the  globular  richness  and  increases  progressively 
under  the  influence  of  repeated  bloodletting.  As  to  the  amount  of 
fibrin,  pneumonia  exerts  the  most  marked  influence,  since  in  this 
disease  it  reaches  the  proportion  of  7.47  per  1000  on  an  average, 
10.5  being  the  maximum.  Even  when  this  disease  occurs  in  indi- 
viduals already  suffering  from  an  affection  which  diminishes  the 
amount  of  fibrin,  such  as  purpura  and  cancer,  pneumonia  gives  rise 
to  an  increase  of  this  substance.  It  is  said  that  albumin  is  dimin- 
ished when  fibrin  increases.  According  to  Becquerel  and  Rodier, 
the  addition  of  these  two  substances  gives  the  normal  total  weight. 

It  would  be  interesting  to  study  the  products  of  disassimilation, 
notably  urea,  ammonia,  and  extractive  matters.  Urea  is  increased 
in  the  blood  mainly  when  the  renal  secretion  is  profoundly  disturbed, 
as  is  the  case  in  cholera  and  variola.  In  cholera  as  much  as  3.6  per 
1000  of  urea  may  be  found.  On  the  other  hand,  when  the  liver  is 
altered  the  extractive  matters  accumulate  in  the  blood. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      303 

The  variations  in  the  amounl  of  glucose  tnusl  tiol  be  overlooked. 
I  have  pursued  on  this  subject  some  experiment!  upon  animals 
inoculated  with  anthrax.  In  operating  upon  cadavers  I  thus  noticed 
that  the  blood  contained  no  glucose.  In  view,  however,  of  the 
rapidity  with  which  sugar  disappears  after  death,  the  experimenl 
was  not  conclusive.  II  blood  is  taken  a1  the  tnomenl  when  the 
animal  succumbs  ;in  r\f icincly  intense  reduction  "I  Pehling'  jolu- 
tion  is  obtained.  During  I  he  firsl  stage  of  anthrax,  while  the  general 
state  of  the  animal  is  apparently  excellent,  the  blood  contains  0.7]  1 
to  1  gram  of  sugar  per  1000.  This  proportion  i-  somewhal  below 
thai  round  in  well-nourished  normal  rabbits,  in  which  it  varies  from 
1.25  to  1.40  grams  per  1000. 

During  the  second  stage,  when  the  anthrax  bacilli  pass  into  the 
blood  and  the  temperature  of  the  animal  is  lowered,  sugar  incri 
in  notable  proportions — it  reaches  the  proportion  of  2.24  and  even 
2.976  grams  per  1000.  This  is  probably  due  to  diminished  con- 
sumption of  sugar,  as  seems  to  be  evidenced  by  the  fall  in  temper- 
ature— another  proof  of  the  decrease  in  nutrition  activity. 

The  chemical  modifications  of  the  blood  explain  the  modifications 
of  its  biological  properties,  viz.,  of  its  action  upon  the  figurate 
elements.  Thus,  the  globulicidal  power  increases  in  pneumonia, 
typhoid  fever,  erysipelas,  and  tuberculosis.  In  certain  experimental 
infections  the  serum  becomes  more  germicidal  than  normal,  even 
when  the  disease  terminates  fatally.  These  questions  will  again 
be  referred  to. 

In  recent  investigations  Achard  and  Gere  endeavored  to  show 
the  pathological  variations  produced  in  the  ferments  of  the  blood 
serum.  These  authors  proved  that  considerable  attenuation  of 
lipase  and  amylase  is  a  serious  symptom  and  often  indicates  approach- 
ing death.  This  result  is  equally  true  with  regard  to  cachectic 
conditions  and  acute  or  chronic  infections,  such  as  pneumonia, 
typhoid  fever,  and  tuberculosis.  Experimental  researches  pursued 
in  our  laboratory  by  Dr.  Clerc  demonstrated  the  development  of 
similar  modifications  in  inoculated  animals.  These  ferments  are 
the  evidences  of  the  activity  of  the  organism.  Their  study  may. 
therefore,  be  useful  for  diagnostic  purposes. 

Microscopic  Study  of  the  Blood.  Microscopic  examination  of  the 
blood  shows  not  only  the  number  and  characters  of  the  corpuscles, 
but  also  reveals  the  mode  of  coagulation  of  the  fibrin  and.  in  some 
measure,  its  quantity.     Hayem  has  given  a  perfect  description  of 


364  1XEE(  Tin  I  -s  J)  I  SEA  SES. 

the  mode  of  coagulation  of  the  blood  in  phlegmasia^,  such  as  pneu- 
monia, and  rheumatism.  Coagulation  is  slightly  retarded.  This 
modification  coincides  with  an  increase  of  the  leucocytes  and  the 
presence  of  phlegmasic  masses  formed  of  "hematoblasts"  which  a 
viscous  substance  unites  with  red  and  white  blood  corpuscles. 

In  the  majority  of  infections  the  number  of  red  blood  corpuscles 
and  "hematoblasts"  is  diminished,  and  this  diminution  becomes 
more  and  more  pronounced  the  longer  the  disease  continues.  The 
red  globules  are  often  altered;  they  contain  less  hemoglobin  than 
under  normal  conditions.  Hence  they  are  lighter  in  color,  and 
some  appear  completely  destitute  of  pigment.  This  occurs  in  cases 
of  adynamic  typhoid  fever,  hemorrhagic  variola,  and  typhopneu- 
monia. 

These  modifications  in  the  red  corpuscles  explain  in  part  the  dis- 
turbance occurring  in  the  respiratory  exchanges  and,  secondarily, 
in  general  nutrition.  In  most  cases  it  is  quickly  repaired.  In 
certain  predisposed  individuals,  however,  reparation  is  incomplete, 
and  infection  is  followed  by  a  more  or  less  persistent  anemia,  at 
times  even  by  chlorosis.  This  occurs  in  consequence  of  the  most 
varied  acute  diseases  as  well  as  in  the  course  of  certain  chronic 
maladies,  such  as  tuberculosis,  malaria,  and  syphilis. 

Variations  of  the  Leucocytes.  Since  attention  was  drawn  to  the 
considerable  role  played  by  the  leucocytes  in  the  protection  of  the 
organism,  great  interest  has  been  aroused  in  the  study  of  the  modi- 
fications which  these  cells  may  undergo.  An  endeavor  was  first 
made  to  determine  their  numerical  variations.  It  has  recently 
been  recognized,  however,  that  this  study  is  insufficient;  the  quali- 
tative modifications  must  be  taken  into  account;  that  is,  the  changes 
occurring  in  the  different  varieties  of  leucocytes  must  be  determined. 

It  may  be  broadly  stated  that  in  the  majority  of  infections 
hyperleucocytosis  is  produced,  which  is  the  more  marked  the  more 
resistant  the  individual.  Under  the  influence  of  the  same  amount  of 
a  given  virus  a  vaccinated  animal  presents  a  more  intense  leuco- 
cytosis  than  an  animal  without  such  experience.  This  result  is 
readily  conceivable  in  view  of  the  protective  role  of  the  white 
blood  corpuscles.  In  fatal  cases  the  number  of  the  leucocytes 
diminishes  as  the  morbid  symptoms  become  aggravated. 

The  number  of  leucocytes  per  cubic  millimetre  being  normally 
from  6000  to  8000,  leucocytosis  is  said  to  exist  when  10,000  are 
counted.     This  figure  is  often  exceeded,  but  it  hardly  ever  rises 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  iNl    H 

above  30,000,  and  bu1  exceptionally  reache  60,000  or  115,000 
was  the  case  in  a  pneumonia  reported  by  Loehr.  Among  infections 
which  most  frequently  give  rise  to  leucocyte  i  '■  may  '-it'-  pneu- 
monia, suppurations  of  all  kinds,  gonorrhea,  and  glander  .  On  the 
oilier  hand,  typhoid  fever  and  measles  cause  bul  a  3ligh1  and  transi- 
tory increase  of  the  leucocytes.  Scarlatina  U  attended  by  a  leuco- 
cytosis  which  persists  long  after  the  fall  of  temperature.  In  tetanus 
leucocytosis  varies  from  15,000  to  20,000.  In  tuberculosis  the 
figures  are  from  10,000  to  20, 000.  When,  however,  m  caseoUE  focus 
breaks  down  and  purulenl  expectoration  supervenes  the  Dumber 
of  leucocytes  at  times  reaches  36,000  (Hayem). 

It  may  broadly  be  stated  thai  leucocytosis  begins,  progresses,  and 
declines  with  the  disease. 

As  to  the  qualitative  modifications  of  the  leucocytes,  it  must  first 
be  noted  that  it  is  mainly  the  neutrophilic  polynuclears  which  are 
increased.  In  gonorrhea  the  eosinophils  are  said  to  increase;  in 
whooping-cough  the  lymphocytes;  in  variola  and  varicella  the 
mononuclears. 

It  is  important  to  determine  for  each  infection  the  numerical 
variations  undergone  by  each  variety  of  leucocytes.1  This  has  been 
done  by  Chantemesse  and  Rev  for  erysipelas.  In  adults  who  recover, 
the  polynuclears  suffer  a  diminution  until  recovery  is  confirmed. 
The  large  mononuclears,  the  number  of  which  does  not  vary  much 
during  the  febrile  period,  increase  considerably  immediately  before 
or  at  the  beginning  of  defervescence.  The  variations  of  the  lympho- 
cytes follow  a  reverse  course,  and  their  increase  is  a  certain  sign  of 
a  positive  cure.  The  eosinophils,  commonly  absent  during  the 
febrile  period,  reappear  at  the  moment  of  defervescence.  In  fatal 
cases  hyperleucocytosis  always  exceeds  12.000  and  is  characterized 
by  a  polynucleosis  which  reaches  or  exceeds  the  proportion  of  92  per 
cent.  The  persistence  or  sudden  return  of  polynucleosis  in  the 
course  of  convalescence  indicates  the  imminence  of  a  relapse.  Thus, 
the  interest  of  this  study  for  diagnostic  purposes  is  considerable. 

The  same  study  with  regard  to  typhoid  fever  has  been  made  by 
Chantemesse,  Millet,  and  Stienon.  At  the  beginning  the  absolute 
number  of  the  leucocytes  is  diminished.  The  polynuclears.  however, 
are  more  numerous  than  normal.  They  constitute  70  or  even  90 
per  cent,  of  the  total  number.     The  lymphocytes  are  diminished. 

1  Consult  the  general  review  by  Josue.  "  Fonnule  hemoleucocytaire  de  quelques  mala- 
dies infeetieuses."    Gazette  des  hopitaux.  December  15,  1900. 


366  INFECTIOUS  DISEASES. 

while  the  eosinophiles  are  almost  entirely  absent.  In  the  second 
stage  the  number  of  leucocytes  is  always  below  the  normal;  the 
number  of  the  mononuclears,  however,  and  particularly  of  the 
Lymphocytes,  rises,  while  that  of  the  polynuclears  diminishes  by 
sudden  falls.  During  convalescence  the  polynuclears  are  not  very 
numerous,  while  the  lymphocytes  increase,  and  the  large  mono- 
nuclears represent  20  to  30  per  cent,  of  the  total  figure.  The  increase 
in  the  number  of  the  eosinophiles  announces  that  convalescence  will 
supervene  within  a  day  or  two.  The  return  to  the  normal  is  subse- 
quently effected  in  a  slow  or  progressive  manner.  Should  some 
inflammatory  complication  occur  it  is  announced  by  a  sudden 
increase  in  the  polynuclears. 

In  this  connection  typhoid  fever  may  be  contrasted  with 
pneumonia,  which,  unlike  the  former,  is  a  disease  characterized  by 
an  abrupt  development.  Numerous  hematological  investigations 
demonstrate  that  the  number  of  leucocytes  rises  suddenly  after  the 
initial  chills.  The  polynuclears  predominate ;  before  the  crisis  they 
reach  80  per  cent.;  on  the  eve  of  crisis  they  rise  to  86  per  cent.,  to 
fall  to  71  per  cent,  after  defervescence  and  to  57  per  cent,  on  the  clays 
following  (Leredde).  At  this  moment  an  increase  in  lymphocytes 
and  eosinophiles  is  observed,  the  latter  rising  from  3  per  cent,  to 
5,  to  6,  or  even  7  per  cent.  (Turck).  In  cases  in  which  polynucleosis 
persists  after  defervescence  the  termination  of  the  disease  should  be 
considered  incomplete.  If  the  polynuclears  increase,  suppuration  of 
the  exudate  is  to  be  feared. 

The  infections  characterized  by  mononucleosis  constitute  a  very 
particular  group.  Aside  from  whooping-cough  (Mennier)  the  patho- 
genic agent  of  which  is  unknown,  we  see  that  all  of  them  are  pro- 
duced by  protozoa.  This  has  first  been  demonstrated  with  regard 
to  malaria.  During  a  paroxysm  there  is  first  an  increase  of  lympho- 
cytes and,  in  a  less  degree,  of  eosinophiles  and  large  mononuclears. 
Fifteen  to  twenty  minutes  later  the  lymphocytes  are  more  numerous 
and  the  large  mononuclears  rarer.  The  polynuclears  undergo  scarcely 
any  change. 

The  author  believes  variola  to  be  due  to  a  protozoon  of  a  quite 
different  order.  Whether  this  parasite  develops  in  man  or  is  inocu- 
lated into  rabbits  it  gives  rise  to  mononucleosis.  Leucocytosis  may 
be  moderate.  In  a  total  of  36  cases,  studied  in  our  wards,  we  found 
19  -times  6000  to  15,000  leucocytes  per  cubic  millimetre,  12  times 
15,000  to  20,000,  3  times  25,000,  and  in  the  last  two  cases  30,000  to 


INFLUENCE  f)E  INFECTIONS  UPON  THE  ORGANISM, 

.'i5, ooo.    Although  leucocytosis  is  present  from  the  beginning,  it  i- 
particularly  intense  at  fche  time  of  vesiculation,  and   remain 
tionary,  slightly  diminishes,  or  increa  e   during pu  tulation.     In  the 
hemorrhagic  Tonus  it  is  less  marked,  bul  i-  3eldom  ab  ent. 

In  scarlatina  the  number  of  the  leucocytes  is,  according  to  Kolshet- 
kofT,  from  10,000  to  20,000  in  lighl  cases,  20,000  to  30,000  in  i 
of  ordinary  intensity,  more  than  30,000  in  grave  cases.    The  poly- 
nuclears  represent  sf>  to  os  per  cent.;  the  eosinophiles,  which  are 

slightly  decreased  at,  the  beginning  of  (he  disease,  grow  more  and 
more  numerous  during  its  course:  they  diminish  and  may  even 
disappear  in  grave  eases. 

Bacterioscopic  Examination  of  the  Blood.  Microscopic  examina- 
tion of  small  drops  of  blood  al  times  reveals  the  presence  of  patho- 
genic agents,  and  thus  gives  valuable  clinical  information.  Such  is 
particularly  the  case  in  malaria — the  presence  of  the  peculiar  hemato- 
zoon  enables  us  to  reach  a  positive  diagnosis.  In  hemorrhagic 
variola,  as  well  as  in  congenital  smallpox,  the  blood  contains 
corpuscles  characteristic  of  this  infection.  The  same  elements  are 
found  in  the  blood  of  inoculated  animals,  at  least  when  the  disease 
evolves  rapidly. 

When  practised  during  a  paroxysm  of  recurrent  fever,  examination 
of  the  blood  reveals  the  presence  of  the  spirilla  of  Obermeier.  The 
parasite  cannot  be  seen  during  the  intervals  of  the  paroxysms. 

The  microscope  more  rarely  permits  the  detection  of  bacteria. 
The  latter  are  hardly  ever  seen  except  toward  the  end  of  disease  3. 
Such  particularly  is  the  case  in  anthrax — the  presence  of  the  anthrax 
bacilli  in  the  blood  indicates  a  general  infection  and  announces  the 
approach  of  a  fatal  termination. 

This  does  not  mean  that  bacteria  do  not  invade  the  blood,  even 
in  cases  of  curable  infections,  but  that  the  germs  are  always  present 
in  such  small  numbers  that  it  is  difficult  to  detect  them  by  a  simple 
microscopic  examination.  To  obtain  precise  information,  cultiva- 
tion and,  sometimes  with  advantage,  inoculation  must  be  resorted 
to.  By  employment  of  these  various  procedures  the  tubercle  bacillus 
has  been  detected  in  the  blood  in  cases  of  acute  miliary  tuberculosis 
(Weichselbaum)  and.  more  rarely,  the  bacillus  of  glanders  and  that 
of  typhoid  fever.  The  latter,  which  is  only  very  exceptionally 
encountered  in  the  blood  of  the  general  circulation,  is  often  met 
with  in  the  rose-colored  spots  of  the  skin  and.  almost  constantly,  in 
the  blood  of  the  spleen. 


368  INFECTIOUS  DISEASES. 

The  microbes  of  septicemia — the  staphylococcus,  streptococcus, 
and  pneumococcus — invade  the  blood  oftener  than  is  generally 
believed,  but  they  are  present  in  such  small  numbers  that  it  is 
difficult  to  detect  them.  When,  however,  a  considerable  amount  of 
the  blood  is  cultivated  or  inoculated  it  is  seen  that  the  microbes 
are  present  in  the  blood  even  in  benign  cases,  although  they  art1 
more  numerous  in  grave  cases.  In  this  respect  the  figures  given  by 
Beco  are  altogether  conclusive.  Of  fifty-six  patients  suffering  from 
pneumonia  eleven  had  the  pneumococcus  in  the  blood.  Of  twenty- 
nine  of  these  patients  who  recovered,  in  only  two  was  the  blood 
invaded.  Among  the  twenty-seven  who  died  the  blood  was  infected 
in  ninety. 

It  is  well  to  add  that  the  staphylococcus  has  also  been  found  in 
the  blood  in  cases  of  furunculosis,  anthrax,  osteomyelitis,  and  puer- 
peral or  surgical  infections.  According  to  Sittmann,  its  presence  does 
not  render  the  prognosis  so  serious  as  does  that  of  the  streptococcus 
or  pneumococcus. 

Modifications  of  the  Hematopoietic  Organs.  Of  the  numerous 
modifications  suffered  by  the  blood  in  the  course  of  infectious  dis- 
eases some  are,  perhaps,  due  to  the  direct  action  of  microbic  toxins, 
but  most  of  them  depend  upon  previous  modifications  of  the  organs 
or  tissues.  The  blood  being  a  production  of  cellular  origin,  its 
changes  indicate  previous  modifications  in  the  organs  concerned  in 
the  task  of  assuring  its  chemical  constitution  or  furnishing  it  with 
figurate  elements.  It  is,  therefore,  natural  to  investigate  the  occur- 
rences in  the  hematopoietic  organs.  For  consideration  of  the  mor- 
phological elements  attention  must  be  drawn  to  the  organs  in  which 
the  red  and  the  white  blood  corpuscles  are  formed — the  bone-marrow, 
spleen,  lymphatic  glands,  and  the  thymus. 

As  a  result  of  the  admirable  researches  of  Ehrlich  it  was  believed 
that  the  hematopoietic  organs  could  be  divided  into  two  groups. 
One  group  is  constituted  by  the  lymphoid  tissue  and  gives  rise  to 
non-granular  mononuclears,  namely,  the  lymphatic  glands,  the 
spleen,  and  the  lymphoid  structures  of  the  digestive  tract.  The 
other  group,  represented  by  the  myeloid  tissue,  is  said  to  be  the 
source  of  red  blood  corpuscles  and  granular  polynuclear  leucocytes. 
So  sharp  a  distinction  is  no  longer  admissible.  The  researches  pur- 
sued by  me  with  Dr.  Josue  showed  that  view  to  be  too  sweeping  as 
regards  the  bone-marrow.  The  histological  examinations  which  I 
made  with  Weil  tend  to  prove  that  the  study  of  variola  does  not 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM. 

confirm  this  dichotomy,  Finally,  in  s  highly  remarkable  eri 
researches,  Dominici  systematically  studied  the  various  hemato- 
poietic organs  of  man  and  animals  and  demon  trated  thai  the  spleen 
may  undergo  a  total  myeloid  transformation,  as  notably  occui 
;i  resull  of  repeated  hemorrhages.  He  further  demonstrated  thai 
vaccine  virus  causes  the  appearance  of  basophilic  and  amphophilic 
myelocytes  and  nucleated  red  blood  corpuscles  in  the  lymphatic 
glands.3  It  may,  therefore,  be  concluded  thai  the  various  lymphatic 
cells  may  originate  in  all  the  organs  concerned  in  hematopoiesis. 
If,  under  normal  conditions,  each  organ  contains  exclusively  one  sorl 
of  leucocytes,  infection  c.'iuses  these  seemingly  fixed  distinctions  to 
disappear.  Thus,  cellular  types,  which  were  no  longerfound  in  the 
adult,  reappear,  indicating  ;i  return  to  conditions  <>f  fetal  life. 

The  Bone-marrow  in  Infections. 

Preliminary  Considerations  of  Normal  Anatomy  and  Physiology. 
The  bone-marrow  has  long  been  considered  a  tissue  filling  up  the 
interior  of  bones  to  give  them  solidity  without  increasing  their 
weight.  It  is  now  known  that  it  discharges  in  the  economy  numerous 
functions  of  importance.  This  new  conception  has  been  accepted 
with  some  difficulty.  In  fact,  the  cellular  elements,  which  evidently 
represent  the  active  part,  diminish  and  disappear  as  the  individual 
grows;  fat  takes  their  place,  so  that  the  marrow  seems  to  lose  all  it- 
functional  importance.  It  comes  to  a  state  of  rest.  As  soon, 
however,  as  a  new  physiological  or  pathological  condition  requiring 
the  production  of  white  or  red  blood  corpuscles  supervenes,  the  fat 
is  absorbed,  the  cells  proliferate,  and  in  some  instances  finally 
become  as  numerous  as  in  young  subjects.  Instead  of  the  yellow 
color  which  the  marrow  presents  in  the  adult,  it  becomes  red.  as  in 
the  beginning  of  life;  it  resumes  the  fetal  character.  Thus,  histo- 
logical examination  may  inform  us  as  to  the  degree  of  activity  of 
the  bone-marrow. 

It  is  known  that  the  bone-marrow  seems  to  be  formed  of  fatty 
tissue  in  the  adult.     A  more  attentive  study  shows,  however,  that 
it  is  a  tissue  of  well-determined  texture.     It  contains  two  serii  - 
cellular  forms;  some  are  destined  for  the  production  of  leucocytes, 
the  other  for  the  production  of  cells  with  hemoglobin. 

1  Dominici.     Sur  le  plan  de  structure  du  systeme  hematopoietique  do?  maim 
Archives  de  med.  exper..  July.  1901. 

24 


370  IXFECTIOUS  DISEASES. 

The  cells  of  the  first  series — i.  e.,  the  myelocytes,  generally  measure 
from  14ft  to  20/*.  have  the  appearance  of  mononuclear  leucocytes, 
but  differ  from  them  by  the  presence  of  protoplasmic  granulations 
similar  to  those  found  in  the  polynuclear  leucocytes  of  the  blood. 
According  to  their  tinctorial  properties  the  granulations  are  divided 
into  oxyphiles  or  eosinophils,  pseudoeosinophiles,  neutrophiles,  and 
basophiles.  The  neutrophil  myelocytes  are  the  most  profusely 
distributed. 

The  bone-marrow  likewise  produces  red  blood  corpuscles.  It  is 
possible  to  follow  the  various  stages  of  the  evolution  of  the  nucleated 
red  globules. 

The  bone-marrow  seems  also  to  be  capable  of  producing,  especially 
under  pathological  conditions,  soluble  substances;  as  the  latter 
always  proceed  from  cellular  secretions,  the  proliferation  observed 
in  the  course  of  diseases  is  favorable  to  this  conception. 

It  is  hardly  necessary  to  recall  the  role  played  by  the  bone-marrow 
in  the  nutrition  and  regeneration  of  bones.1  Finally,  the  marrow 
is  capable  of  absorbing  as  well  as  of  secreting.  The  experiments  of 
Dubuisson-Christot  demonstrated  that  substances  introduced  into 
the  medullary  canal  of  long  bones  rapidly  pass  into  the  general 
circulation,  even  more  rapidly  than  when  injection  is  made  into  the 
peritoneum  or  the  liver. 

Modifications  of  the  Bone-marrow  in  Experimental  Infections. 
The  bone-marrow  becomes  the  centre  of  defense  for  the  organism  in 
a  number  of  infections  and  intoxications.  This  role,  which  we 
endeavored  to  elucidate  in  a  series  of  researches  published  with 
Dr.  Josue,  had  but  rarely  been  studied  before  us.  In  December, 
1896,  we  reported  our  first  investigations  on  the  state  of  the  bone- 
marrow  in  suppurations,  pointing  out  the  important  modifications 
in  the  structure  and  texture  of  this  tissue.2  Dominici,3  proving 
the  appearance  of  nucleated  red  globules  in  the  blood  of  infected 

1  Oilier.  De  la  moelle  cles  os  et  de  son  role  dans  1 'ossification.  Journal  de  la  phys- 
iologic 1863.  Goujon.  Recherches  expeximentales  sur  les  propri£t£s  physiologiques  de 
la  moelle.     Journal  d'anatomie  et  de  physiologie,  1869. 

2  Roger  and  Josue\  Recherches  experimentales  sur  les  modifications  de  la  moelle 
osseuse  dans  les  suppurations.  Soc.  de  biol.,  Dec.  12,  1896,  p.  1038.  Action  de  la  toxine 
et  de  l'antitoxine  diphteriques  sur  la  moelle  osseuse,  ibid.,  Jan.  9,  1897.  Des  modifi- 
cations histologiques  et  ehimiques  de  la  moelle  osseuse  aux  differents  ages  et  dans 
l'infection  staphylococeique,  ibid.,  March  25,  1899.  Des  modifications  histologique 
ehimiques  de  la  moelle  osseuse  dans  l'inanition,  ibid.,  May  5,  1900. 

3  Dominici.  Tumeur  de  l'ampoule  de  Vater.  Soc.  anat.,  1S96,  p.  708.  Septicemic 
exp.  a  globules  rouges  nucleus,  ibid.,  1896,  p.  714. 


INFLUENCE  OF  INFECTIONS  UPOH   THE  ORGANISM,      ;;71 

rabbits,  attributed  this  phenomenon  to  the  reaction  oi  the  bone- 
marrow.  About  the  same  time  Trambu  ti  tudied  tli*'  bone-marrow 
of  guinea-pigs  in  diphtheria  and  laid  Jtre  on  the  igne  of  functional 
activity  which  this  disease  imposed  upon  the  cellg  of  the  marrow. 

The  reaction  of  the  bone-marrow  is  expre*  ed  not  only  by  cellular 
modifications  indicating  increased  activity,bu1  also  by  topographic 
changes  easily  noticeable  on  sections,  even  when  examined  by  the 
unassisted  eye.  The  marrow  gives  rise  to  blood  cells  endowed  with 
phagocytic  properties ;  consequently,  when  an  increased  numbei  ol 
these  is  required,  the  original  cells  or  myelocytes,  intermediate 
forms,  even  the  polynuclears,  are  likewise  increased  in  the  medullary 
tissue.    The  latter  is  thus  invaded  by  a  tremendous  number  of  cells. 

By  giving  birth  to  the  leucocytes,  which  will  pick  up,  digest,  and 
destroy  pathogenic  germs,  the  bone-marrow  plays  a  rdle  of  prime 
importance  in  the  defense  of  the  organism;  it  supplies  it  with  the 
army  which  will  defeat  the  invaders.  It  is,  therefore,  a1  the  momenl 
of  clanger  that  this  tissue1  displays  the  greatest  energy. 

The  role  of  the  bone-marrow  thus  seems  to  be  more  complex. 
Although  there  is  no  direct  demonstration,  it  is  highly  probable  that 
the  marrow  possesses  secretory  and  antitoxic  properties.  This  is 
indicated  by  the  multiplication  of  medullary  cells  in  the  course 
of  various  intoxications  and  consecutively  to  the  introduction  of 
certain  sera. 

This  reaction  of  the  bone-marrow  is  observed  in  a  great  number 
of  conditions.  Staphylococcic  infection,  which  was  the  first  subject 
of  our  investigations,  may  be  cited  as  an  example. 

Modifications  in  the  Bone-marrow  in  Experimental  Staphylococcic  In- 
fection. In  these  experiments  we  employed  adult  rabbits  weighing 
from  2000  to  3200  grams.  We  chose  such  heavy  animals  in  order  to 
be  certain  that  their  marrow  presented  the  adipose  type.  In  fact, 
it  is  known  that  the  cellular  elements,  which  are  very  abundant  in 
the  young,  diminish  with  age  and,  in  the  adult,  are  replaced  by  fat. 

If  a  culture  of  medium  virulence  be  employed  the  modifications 
which  result  from  a  subcutaneous  injection  may  easily  be  watched 
in  the  bone-marrow.  Forty-eight  hours  after  the  injection  of  1  c.c. 
of  the  culture,  the  local  lesion — i.  e.,  suppuration — appears.  At  this 
moment  leucocytosis  is  at  its  maximum:  the  leucocytes  are  found 
to  number  from  12,000  or  15.000  to  30.000  or  40.000  per  c.mm.  If 
the  animal  is  killed  the  bone-marrow  presents  a  red  color,  con- 
siderable congestion,  and  multitudes  of  red  cells.     The  medullary 


372 


IXFECTIO  US  DISEASES. 


cells  are  also  increased  and  particularly    profuse  in  the  peripheral 
parts. 

The  modifications  progress  so  that,  on  the  fifth  day,  the  marrow 
is  constituted  simply  of  cells  mixed  with  red  corpuscles  and  accumu- 


Fig.  21. 


Bone-marrow  of  a  normal  rabbit.  On  the  left  side,  the  sinus  with  its  artery;  on  the 
right,  the  cortical  layer.  At  the  centre,  the  areolar  tissue  containing  a  small  number 
of  cells. 

Fig.  22. 


Bone-marrow  of  the  rabbit  in  neutrophilic  reaction.     Considerable  increase  in  the 
number  of  cells;  diminution  in  volume  of  fatty  areolre. 


fated  in  large  numbers  at  certain  points.     There  is  nothing  left  of 
the  normal  arrangement,  no  more  areolae  full  of  fat. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      ;;7.; 


At  the  end  of  fifteen  days  rel  rogre  ion  of  the  proce  i  observable; 
the  normal  conditions  tend  to  reappear  here  and  there)  areolae  full 
of  fat  are  again  found,  remarkable  only  for  their  smaller  dimension  , 

To  sum  up,  all  the  cellular  elements  Lncrea  e  in  number  and    \/< 
they  are  in  a  state  of  intense  activity.    The  inerl  elements,  which, 
under  normal  conditions  or  rather  in  a  state  of  rest,  form  the  gre 
part"  of  the  tissue,  give  way  to  the  active  elements. 

A  question  may  be  raised  here:  May  one  variety  of  celU  multiply 
in  :i  predominanl  or  exclusive  manner?  In  other  words,  are  there 
neutrophilic,  eosinophilic,  or  normoblastic  reactions? 

In  the  lii'si  place,  it  is  to  be  recognized  thai  there  is  never  an 
absolutely  exclusive  multiplication  of  cells.  In  the  cases  which  we 
examined  a  certain  degree  of  irritation  and  proliferation  of  other 
species  existed.  Likewise,  in  the  neutrophilic  reaction  of  suppura- 
tions and  certain  infections  there  is  multiplication  of  other  varieties 
of  cells. 

I  i.;.  23. 


Bone-marrow  of  normal  man.    Sinus  containing  an  artery.     Few  cells.     Fatty  areoUe 

of  large  size. 

Reactions  of  the  Bone-marrow  in  Man.  The  human  bone- 
marrow  seems  to  lose  most  of  its  activity  at  an  early  age.  When, 
however,  an  intoxication  occurs  it  again  assumes  the  type  observed 
in  childhood :  it  resumes  its  functions  in  order  to  protect  the  organism. 
The  cellular  elements,  which  were  extremely  rare  when  the  organs 
were  not  engaged  in  struggle,  become  very  numerous.     The  reac- 


374 


IXFECTIO  US  DISEASES. 


tion,  however,  is  less  readily  produced  and  less  marked  than  in  the 
rabbit. 

Let  us  take,  for  example,  the  neutrophilic  reaction  of  the  bone- 
marrow  in  tuberculosis.1  The  proliferated  bone-marrow  is  darker 
in  color,  softer,  and  at  times  pasty.  Under  the  microscope  it  is  seen 
that  cellular  proliferation  is  not  at  once  progressing  throughout  the 
entire  thickness  of  the  marrow.  The  invasion  by  the  cells  is  at  first 
partial;  their  distribution  is  not  clearly  systematic.  Even  in  the 
midst  of  proliferated  parts  there  may  be  found  fatty  areolae,  though 
not  so  large  as  normal. 

Fig.  2-4. 


dj 


Human  bone-marrow  in  neutrophilic  reaction.  Enormous  increase  in  the  number  of 
cells ;  the  areola?  are  far  less  numerous  and  voluminous  than  normally.  (Compare  with 
Fig.  23.) 

When  considerably  magnified  all  the  cells  are  found  to  be  in- 
creased in  number,  although  the  neutrophile  myelocytes  are  pre- 
dominant, mixed  with  all  the  intermediate  series  ending  in  poly- 
nuclears.  The  giant  cells  are  not  as  large  as  in  the  rabbit.  In  the 
midst  of  all  these  elements  are  observed  masses  of  pigment  colored 
black  by  ammonium  sulphydrate. 

The  Bone-marrow  in  Smallpox.  The  recent  epidemic  of  variola 
in  France  offered  an  opportunity  to  take  up  this  study  and,  by  means 
of  numerous  improvements  in  fixation  and  staining,  to  complete  and 


1  Josue.    Moelle  osseuse  des  tuberculeux  et  histogenfese  du  tubercule.    These  de  Paris, 
1898. 


TNFLUKNdK  or  ISFMJTI0XT8  UPON  THE  ORG  I     I    v.      375 

modify  in  some  respects  the  result  alr<  ady  obtained.    The  re  1  archee 
of  Dr.  Courmonl  and  Montagard1  pursued  coincidently  with  1 
and  published  only  three  weeks  after  our  firsl  note,2  confirm  the 
principal  facts  se1  fori  h  by  us. 

In  two  cases  of  variola  we  noticed  an  absence  of  medullary  reaction. 
This  is  an  exception.  Ai  all  events,  however,  the  reaction  of  the 
bone-marrow  manifests  little  intensity,  ai  leasl  in  the  adult.    Our 

Fig   25, 


Section  of  bone-marrow  in  variola.    Moderate  proliferation  of  cells 

surrounding  the  vessels. 


confined  to  the  area 


observations  on  this  point  are  at  variance  with  those  of  Golgi.3  who 
laid  stress  upon  the  intensity  of  the  reactionary  phenomena  which 
the  bone-marrow  presented  in  the  cases  studied  by  him.  However, 
by  comparing  the  results  furnished  by  a  topographic  examination 
of  the  marrow  with  those  obtained  by  counting  The  white  corpuscles 


1  Courmont  and  Montagard.     La  moelle  osseuse  dans  la  variole.     XlTle  Cong     - 
international  de  medecine.  Section  de  path,  generate.  Paris.  August.  1900.  p.  L87 

2  Roger,   Josue.   and  Emile  Weil.     La  moelle  osseuse  dans  la  variole.     Soe.  anat. 
July  13,  1900.     Archives  de  rued.  exp..  September.  1900. 

3  Golgi.    Sulle  alterazioni  del  midollo  del  ossa  nel  vainolo.  Rivista  elinica  di  Bologna, 
1873,  p.  238. 


376  IXFECTIO  US  DISEA  SES. 

on  the  eve  of  death  we  find  an  absolute  concordance.  Though  the 
proliferation  of  the  cells  is  poorly  marked  or  nil  in  the  medullary 
tissue,  the  number  of  leucocytes  contained  in  the  blood  itself  is  not 
great,  varying  from  6000  to  S000,  not  exceeding  442S  in  cases  of 
confluent  variola  with  terminal  hemorrhages  in  which  the  bone- 
marrow  was  fatty. 

The  appearance  of  the  bone-marrow  in  children  suffering  from 
variola  is  altogether  different.  The  latter  were  all  attacked  by 
bronchopulmonary  infectious  complications.  The  marrow  was  red 
and  invaded  by  large  numbers  of  cells.  The  fatty  areolae  had  com- 
pletely disappeared.  The  cellular  formula  in  smallpox  may  be 
briefly  laid  down  as  follows:  marked  predominance  of  the  mono- 
nuclears, relative  diminution  of  the  polynuclears.  This  is  in  accord 
with  the  findings  of  a  qualitative  examination  of  the  blood,  in  which 
the  polynuclears  are  likewise  present  in  small  numbers,  while  the 
mononuclears  are  more  abundant  than  normally,  and  belong  in  part 
to  different  varieties  which  are  not  found  under  normal  conditions: 
myelocytes,  forms  of  irritation  of  Tiirck,  etc. 

The  reactionary  manifestations  are  the  same  in  both  pustular  and 
hemorrhagic  variola. 

Lesions  of  the  Bone-marrow  in  Infections.  Apart  from  those 
modifications  which  occupy  the  undecided  boundary  between 
healthy  and  diseased  conditions,  since  they  indicate  a  struggle 
against  a  pathogenic  agent,  true  lesions  may  also  be  observed  in  the 
medullary  tissue. 

An  alteration,  particularly  frequent  in  acute  infections,  is  char- 
acterized by  disappearance  of  the  nucleus,  so  that  the  cell  forms  no 
more  than  a  uniform  red  mass.  Such,  for  instance,  is  the  case  in 
experimental  infection  by  anthrax. 

There  may  also  be  found  lesions  of  the  connective  tissue.  Among 
these  sclerosis  is  the  most  frequent.  The  sclerotic  marrow  often 
observed  in  tuberculous  individuals  may  be  taken  as  a  type.  It  is 
yellow  in  color  and  firm.  Sclerosis  often  coexists  with  cellular 
proliferation;  the  two  lesions  are  then  sharply  separated  and  are 
produced  in  different  regions  of  the  medullary  tissue. 

The  vessels  at  times  present  marked  lesions  of  arteritis  and 
phlebitis.  In  five  children  who  suffered  from  chronic  gastroenteritis 
and  succumbed  to  bronchopneumonias,  Haushalter  and  Spillmann 
found  marked  lesions  of  endarteritis  and  periarteritis. 

Finally,  miliary  tubercles  may  develop  in  the  medullary  tissue  in 


INFLUENCE  OF  INFECTIONS  UPON  THE  0BQANI8M.       ;;?? 

oases  of  acute  tuberculosis.    These  tubercle    pr<  enl  the  ordh 
structure,  and  may  be  reproduced  experimentally  by  inoculating 
cultures  of  the  tubercle  bacillus  into  the  bone-marrow. 

Semiology  of  the  Bone-marrow.  The  study  of  modifications  in 
the  bone-marrow  presents  considerable  importance  from  the  stand- 
point of  general  pathology.  It  reveals  one  of  the  defen  ive  pro- 
cedures of  the  organism.  It  may  appear  less  interesting  from  a 
clinical  standpoinl .  The  increased  activity  of  the  bone-marrow  o 
however,  explain  certain  painful  sensations  experienced  in  the  course 
or  in  consequence  of  infections  in  the  limbs,  especially  in  the  ju 
epiphysial  regions.  It  likewise  accounts  for  the  overgrowth  of  young 
subjects  in  consequence  of  certain  diseases,  notably  typhoid  fi 
It  may  even  be  questioned  whether  certain  osseous  deformities, 
certain  lesions  of  the  skeleton,  are  not  the  consequence  of  the  morbid 
process  of  which  the  bone-marrow  is  the  sent.  Are  nol  the  osteop- 
athies of  pneumonia,  the  osseous  lesions  of  dyspeptic  persons,  and 
notably  the  nodules  of  the  second  phalanges,  connected  with  lesions 
of  the  medullary  tissue?  Is  not  this  tissue  responsible  for  the 
development  of  rachitis  and  osteomalacia? 

That  these  remarks  are  not  baseless  is  shown  by  the  results  yielded 
by  the  study  of  typhoid  fever.  Various  osteomedullary  manifes- 
tations have  been  observed  as  a  result  of  this  infection.1  Among 
the  milder  phenomena  are  the  dull  pains  similar  to  those  felt  in  the 
so-called  "fever  of  growths."  It  is  probably  due  to  the  action  of 
diffused  toxins.  At  a  higher  degree  the  patient  complains  of  a  fixed 
pain  which  is  the  clinical  expression  of  a  microbic  colonization. 
Either  resolution  occurs  or  an  exostosis  develops.  Finally,  if  the 
microbe  is  more  virulent,  a  focus  of  osteomyelitis  is  produced,  at 
times  so  slowly  as  to  simulate  a  cold  abscess. 

A  similar  series  of  evolution  is  observed  in  a  chronic  infection, 
viz.,  syphilis.  Pains  in  the  bones,  exostoses,  and  gummata  equally 
point  to  an  important  participation  of  the  medullary  tissue. 

The  osteomedullary  tissue  may  be  the  starting  point  of  embolic 
accidents.     Osteomyelitis,  proliferative  inflammations  of  the  bone- 
marrow,  liberate  a  certain  amount  of  fat.    This  substance  enters  the 
circulation,  and,  being  arrested  in  the  capillaries,  notably  in  th<  »s 
the  lung,  may  give  rise  to  grave  disorders. 

The  clinical  study  of  the  bone-marrow  must  be  completed  by 

Achard.    Manifestations  osseuses  de  la  fievre  typhoi.de.    Semaine  m&L,  18 


378  I SFECTIOUS  DISEASES. 

hematological  examinations.  These  examinations,  by  showing  a 
great  number  of  myelocytes,  enable  us  to  affirm  involvement  of  the 
marrow.  Two  diseases  in  particular  cause  the  passage  into  the 
blood  of  these  peculiar  cells,  which  are  never  encountered  therein 
under  normal  conditions.  One  of  them  is  lymphadenia,  the  influence 
of  which  has  long  been  known;  the  other  is  variola,  which  gives  rise 
to  a  myelocytosis  so  very  characteristic  that  it  may  aid  in  establish- 
ing a  differential  diagnosis. 


\^' 


The  Spleen  in  Infections. 

The  important  role  played  by  the  spleen  in  the  defense  of  the 
organism  has  only  recently  been  understood.  It  appears  now 
demonstrated  that  this  gland  exerts  a  destructive  action  upon  living 
parasites  and  organic  particles.  Its  chief  function,  however,  is  to 
supply  to  the  circulation,  and  thus  send  to  distant  parts  of  the 
economy,  cells  capable  of  struggling  against  infectious  agents.  In 
addition  to  this  phagocytic  role  related  to  its  richness  in  morpho- 
logical elements,  the  spleen  may  also  aid  in  modifying  the  chemical 
constitution  of  the  blood;  it  produces  germicidal  substances.  This 
protective  role,  however,  important  as  it  is,  cannot  be  said  to  be 
indispensable  for  the  economy.  Animals  devoid  of  a  spleen  are  still 
capable  of  resisting  infection,  because  there  are  many  other  organs 
endowed  with  the  same  function.  We  shall  cite  but  one  example: 
In  variola,  the  reactionary  modifications  in  the  bone-marrow  and 
in  the  spleen  are  analogous;  the  same  cells  are  produced  by  both 
organs. 

Infectious  diseases  almost  constantly  affect  the  spleen  and  in 
most  cases  cause  hypertrophy  of  this  organ.  This  law  suffers  a  few 
exceptions.  The  liver  is  not  altered,  at  least  its  volume  is  not 
increased,  in  yellow  fever,  dysentery,  and  cholera;  it  is  possible, 
however,  that  its  parenchyma  does  undergo  modifications  which 
require  minute  investigations  for  their  discovery. 

The  state  of  the  spleen  in  typhoid  fever  has  been  a  subject  of 
particular  attention.  Morgagni  noted  the  hypertrophy  of  this  organ 
in  the  course  of  febrile  diseases  which  may  easily  be  related  to 
typhoid  fever.  Some  authors  went  so  far  as  to  regard  the  alteration 
of  this  gland  the  characteristic  feature  of  typhoid  fever,  and  described 
epidemic  and  contagious  splenitis.  It  is  to  be  remarked,  however, 
that  the  spleen  is  not  alone  altered,  but  the  other  hematopoietic 
glands  are  similarly  involved. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM       379 

As  is  known,  hypertrophy  of  the  spleen  occui  in  the  middle  ol 
the  first  week  of  typhoid  \'c\cv;  it  increases  until  the  end  of  the 
second  week,  und  may  be  accompanied  by  intraparenchymatoufl 
hemorrhages  and  terminate  exceptionally  in  rupture  of  the  organ. 
The  hypertrophied  spleen  is  al  firsl  firm,  hard,  and  red.  At  thu 
stage  the  dominanl  feature  is  congestion  of  the  parenchyma,  which 
is  so  intense  at  certain  points  as  to  produce  small  hemorrhagic  foci. 
The  cellular  lesions  are  not  pronounced.  Siredey  noted  only  a 
multiplication  of  the  cells  of  the  Malpighian  corpuscles.  In  the 
second  stage — i.e.,  from  the  twelfth  to  the  thirtieth  day  -the  spleen 
in  some  cases  remains  firm  and  hard  ;  oftener  it  i-  -<>i't .  and  "n  section 
it  presents  small  points  which  are  due  to  the  prominence  "I'  the 
corpuscles  of  Malpighi.  The  latter  contain,  as  normally,  lympho- 
cytes. This  variety  is  mixed,  however,  with  numerous  mono- 
nuclear and  even  polynuclear  cells.  The  cells  of  the  pulp  are  tume- 
fied, voluminous,  and  generally  filled  with  the  detritus  of  red  and 
white  blood  corpuscles.  They  have  the  characters  of  mononuclears, 
with  a  small  nucleus  situated  at  one  of  the  poles  of  the  cell.  Finally, 
the  pulp,  like  the  corpuscles,  contains  nodules  formed  of  necr 
cells. 

These  modifications,  some  of  which  represent  reactions  and  others 
lesions  of  the  organs,  are  not  peculiar  to  typhoid  fever:  they  are 
encountered,  in  various  degrees,  in  the  most  varied  infections,  even 
in  those  which  remain  local.1 

Among  the  infections  which  most  frequently  give  rise  to  hyper- 
trophy of  the  spleen  we  may  cite  typhus  fever,  acute  tubercul 
and  the  eruptive  fevers,  notably  scarlatina. 

Special  mention  is  due  to  variola.  Since  the  researches  of  Golgi 
and  of  Ponfick  it  is  generally  admitted  that  the  appearance  of  the 
spleen  is  not  the  same  in  the  suppurating  and  the  hemorrhagic  types 
of  this  infection.  The  organ  is  said  to  be  hypertrophied  in  the 
former,  while  in  the  latter  it  is  believed  to  be  small,  hard,  and  black. 
The  examinations,  however,  made  by  Dr.  Weil  and  myself  during 
the  last  epidemic  render  this  conclusion  inadmissible.  The  hyper- 
trophy of  the  spleen  is  related  not  to  the  clinical  type,  but  to  the 
intensity  of  reaction.  For  this  reason  it  is  more  frequent  in  the 
suppurating  type.  Thus  in  sixteen  fatal  cases  of  confluent  variola 
the  spleen  was  hypertrophied  sixteen  times.     In  twelve  cases  of 

1  Bezancon.  Contribution  a  l'eaule  de  la  rate  dans  les  maladies  infectieuses.  These 
de  Paris,  1S95. 


380  IXFECTIO  US  DISEASES. 

hemorrhagic  variola  it  was  hypertrophied  but  four  times.  In  none 
of  the  latter  scries,  however,  have  we  found  any  peculiar  appearance. 
Contrary  to  Golgi's  opinion,  histological  examination  revealed  no 
f  inii  lamental  differences.  What  is  truly  characteristic  of  hemorrhagic 
variola  is  the,  presence  of  nucleated  red  globules.  In  brief,  the 
modifications  undergone  by  the  cells  of  the  spleen  are  similar  to 
those  observed  in  the  other  hematopoietic  organs,  notably  in  the 
bone-marrow.  Under  the  influence  of  variola  the  spleen  is  thus 
found  to  contain  cellular  elements  which  exist  there  only  during 
fetal  life  and  which  seemed  to  have  disappeared  forever  shortly 
after  birth.     Infection  has  revived  a  past  state. 

Gerhardt  has  shown  hypertrophy  of  the  spleen  to  be  of  frequent 
occurrence  in  pneumonia.  The  same  may  be  observed  in  erysipelas, 
which  resembles  pneumonia  in  certain  features  of  its  evolution. 
Finally,  the  spleen  is  small  in  the  algid  period  of  cholera;  it  becomes 
voluminous  if  typhoid  manifestations  supervene. 

Chronic  infections  do  not  spare  this  gland.  It  will  suffice  to  refer 
to  what  occurs  in  syphilis  during  the  secondary  period,  and  more 
especially  in  malaria. 

It  is  well  to  note  that  in  all  the  organs  and  tissues  in  which  pig- 
ment is  encountered  the  latter  is  found  in  the  vessels.  In  the  spleen 
and  bone-marrowr,  however,  the  pigment  occupies  the  cells.  It  is 
in  these  localities  that  it  seems  to  take  its  origin  at  the  expense  of 
red  blood  globules  altered  and  destroyed  by  the  hematozoa  of 
malaria.1  In  this  connection  recurrent  fever  deserves  special  men- 
tion. During  the  periods  of  apyrexia  the  spirilla  accumulate  in  the 
spleen,  while  the  other  viscera  are  free  from  them.  Metchnikoff 
and  Soudakewitch,2  who  pursued  researches  on  monkeys,  have  seen 
the  parasites  devoured  by  the  macrophages  of  the  spleen.  This  is 
a  highly  remarkable  example  of  phagocytosis.  This  result  seems 
to  be  confirmed  by  the  experiments  of  Soudakewitch,  who  learned 
that  monkeys  deprived  of  their  spleens,  unlike  normal  monkeys, 
succumbed  to  inoculation  of  the  spirilla.  This  has  been  contradicted 
by  Tiktine,  who  repeated  the  experiments  and  denies  all  influence  to 
splenectomy.  He  thinks  that  the  different  results  obtained  by  the 
former  experimenter  are  due  to  the  fact  that  he  operated  in  winter, 
when  the  slightest  lesion  is  sufficient  to  cause  death  to  monkeys. 

1  Kelsch  and  Kiener.     Trait6  des  maladies  des  pays  chauds.     Paris,  1SS9. 

2  Soudakewitch.  Recherches  sur  la  fievre  r6currente.  Annales  de  PInstitut  Pasteur, 
1891,  p.  515. 


INFLUENCE  OF  INFECTIONS  UPOh  THE  ORGANISM.       :>,*) 

The  highly  Interesting  work  of  Courmonl  and  Duffau1  teach* 
that  the  resistance  of  animal  varie  con  iderably  according  to  the 
microbe  employed  and  the  time  elapsed  ince  the  extirpation  of  the 
spleen,  [f  the  pyogenic  staphylococcus  i  employed  the  extirpation 
first  diminishes  the  resistance  of  the  animate  rabbits,  dogs,  etc.; 
subsequently  ii  increases  it.  Willi  the  streptococcus  the  results 
are  diametrically  opposed  to  the  former:  animate  in  which  the  spleen 
had  been  extirpated  two  to  eighl  days  proved  more  resistanl  than 
the  controls;  on  the  contrary,  those  which  were  operated  upon 
twenty-seven  to  forty-eighl  days  after  splenectomy  proved  t"  be 
more  susceptible  Lastly,  with  the  bacillus  pyocyaneus  the  animate 
operated  upon  succumbed  more  rapidly  whatever  the  date  of  o] 
tion.  These  experimental  facts  indicate  once  more  tin'  danger  of 
hasty  generalizations  and  explain  a  certain  number  of  contradictory 
results. 

Role  of  the  Spleen  in  the  Production  of  Germicidal  Substances. 
In  order  to  explain  tin1  action  of  the  spleen  upon  microbes  the 
modifications  in  phagocytosis  were  first  invoked.  Such  was  the 
opinion  of  Gamaleia.  The  same  view  was  held  by  Bardach.  A-  i- 
known,  the  latter  author  contends  that  extirpation  of  the  spleen 
lessens  the  resistance  of  animals  by  suppressing  an  important  centre 
of  microbic  destruction.  He  finds  confirmation  of  his  ideas  in  the 
following  experiment:  He  injected  charcoal  powder  into  the  veins 
of  four  dogs.  Two  days  later  he  inoculated  the  animals  with  1  c.cm. 
of  an  anthrax  culture;  all  the  dogs  succumbed,  and  microscopic 
examination  demonstrated  that  the  cells  of  the  spleen,  liver,  and 
bone-marrow  were  crowded  with  charcoal  particles,  and  therefore 
were  absolutely  incapable  of  ingesting  the  microbes. 

At  the  time  these  first  researches  were  published  the  protective 
action  of  the  blood  serum  was  scarcely  recognized.  Since  innumer- 
able investigations  demonstrated  beyond  doubt  the  importance  of 
germicidal  properties  of  the  fluids  of  the  organism,  the  question 
concerning  the  spleen  has  been  taken  up.  The  researches  of  Hankiir 
proved  the  presence  in  the  spleen  of  a  strongly  germicidal  globulin. 
Montuori  next  undertook  this  new  problem.3  and  reported  highly 

1  Courmont  and  Duffau.  Du  role  de  la  rate  dans  les  infection.-.  Archives  de  m<ki. 
expe>im..  1S9S.  p.  431. 

2  Hankin.     A  bacteria-killing  globnline.     Proc.  Roy.  Soc.  London,  xlviii.  p.  93. 

3  Montuori.  Influenza  dell  ablazione  della  mitza  sur  potere  microbicida  del  sangue. 
La  Riforma  med..  1S93.  i.  p.  472  and  4S.3. 


:  i  s  2  I NFE  CTIOl  rS  JDISEA  SES. 

interesting  facts  which  throw  light  on  many  obscure  points.  His 
experiments  demonstrated  the  hematopoietic  function  of  the  spleen. 
This  gland  may.  however,  be  supplemented  by  other  organs,  since, 
a  few  months  after  extirpation  of  the  spleen,  the  blood  regains  its 
germicidal  power.  Montuori  completed  his  experiments  by  investi- 
gating the  chemical  modifications  which  occur  in  the  blood  of  animals 
with  extirpated  spleens.  He  recognized  that  the  bactericidal  power 
of  the  normal  blood  is  due,  as  was  shown  by  Ogata,  to  a  true  ferment. 
This  ferment,  which  is  very  abundant  in  the  blood  of  the  spleen,  is 
absent  from  the  blood  which  has  lost  its  germicidal  power  as  a  result 
of  splenectomy. 

While  animals  deprived  of  the  spleen  are  more  sensitive  to  certain 
viruses,  they  become  more  resistant  to  others.  In  the  latter  case 
the  germicidal  power  of  the  blood  increases  and  acquires  the  property 
of  depriving  microbes  of  their  virulence.  By  making  comparative 
cultures  of  the  staphylococcus  in  the  blood  of  normal  animals  and 
others  without  spleens  Courmont  and  Duffau  established  that  the 
microbe  develops  better  and  becomes  exalted  in  the  serum  of  those 
animals  in  which  the  spleens  were  extirpated.  With  the  strepto- 
coccus the  results  were  reversed;  the  microbe  was  attenuated.  On 
the  other  hand,  Blumreich  and  Jacoby  found  that  the  serum  of 
splenectomized  animals  diminished  the  virulence  of  pyocyaneus 
diphtheria  and  cholera  bacilli,  and  this  power  of  the  blood  accounts 
for  the  increased  resistance  observed  w^hen  splenectomized  animals 
are  inoculated.  It  is  to  be  noted,  however,  that  the  chemical  modi- 
fications of  the  fluids  are  not  the  only  factors  to  be  taken  into  account; 
the  authors  attribute  an  important  influence  to  the  increased  leuco- 
cytosis  which  coincidently  takes  place. 

The  Lymphatic  Glands  in  Infections. 

The  lymphatic  system  is  provided  with  numerous  protective 
organs,  close  follicles,  and  ganglia,  which  seem  to  play  a  double  role : 
to  arrest,  retain,  and  modify  the  figurate  elements  and  soluble 
products  brought  to  them  by  the  lymphatic  capillaries ;  to  pour  into 
the  blood  cells  and  soluble  products  useful  for  the  organism.  In 
order  to  fulfil  their  functions  the  follicles  and  ganglia  are  arranged 
in  chains,  and  are  most  numerously  supplied  to  those  regions  most 
liable  to  microbic  invasions.  They  are  relatively  less  numerous  at 
the  root  of  the  limbs,  especially  of  the  upper  extremities.  Their 
number  in  the  lower  extremities  is  particularly  multiplied  with  a 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM. 

view  to  protect-  the  economy  against  the  bacteria  coming  by  way 
of  the  externa]  genital  organs  and  margin  of  the  anus.  Lik< 
the  follicles  at  the  base  of  the  tongue,  pharynx,  and  ton  il  form  a 
lymphatic  ring  with  the  function  of  combating  the  bacteria  of  the 
mouth  and  throat,  Less  abundanl  in  the  esophagi]  and  th<- 
stomach,  the  lymphoid  organs  are  distributed  with  greal  profusion 
throughout  the  intestine,  where  they  constitute  the  solitary  follicles 
and  Peyer's  patches.  In  the  appendix,  which  is  mosl  liable  to 
attacks  of  infections  agents,  the  lymphoid  system  is  in"-'  richly 
developed,  forming  :i  veritable  glandular  mass  which  has  justly  been 
compared  to  the  tonsil. 

Beyond  this  first  line  of  defense  are  Bituated  the  glands,  which 
represent  as  many  fortresses  ranged  one  behind  the  other.  I'  i- 
.inl  cresting  to  note  that  their  number  is  in  proportion  to  the  danger 
of  infection  in  each  region. 

The  multiplication  of  the  ganglia  around  the  bronchi,  a1  the  rool 
of  the  lungs,  and  especially  in  the  mesentery,  is  particularly  notable. 

In  a  great  number  of  circumstances  bacteria  of  all  kinds  may  pass 
through  the  skin  and  particularly  the  mucous  membranes.  They 
are  arrested  by  the  ganglia,  in  which  they  sojourn  without  giving 
rise  to  any  reaction  or  disturbance.  Loomis  and  Pizzini  discovered 
tubercle  bacilli  in  the  tracheobronchial  and  mesenteric  gland-  of 
apparently  normal  individuals.  Manfredi  and  Perez1  examined  the 
lymphatic  glands  in  eighty-five  animals  and  detected  bacteria  in 
seventy-five  of  them.  The  same  researches  made  upon  three  human 
cadavers  gave  positive  results  in  each  case.  The  subcutaneous 
glands  are  those  most  commonly  infected :  next,  the  tracheobronchial 
glands,  while  the  mesenteric  glands  are  generally  sterile.  Among 
the  species  most  frequently  met  with  are  various  sarcinae,  the  staphy- 
lococcus aureus  or  albus,  the  mesenteric  bacillus,  a  pseudotyphoid 
bacillus,  etc. 

The  microbes  enclosed  in  the  lymphatic  glands  undergo  notable 
alterations.  Manfredi  demonstrated  that  they  gradually  lose  their 
virulence  and  are  finally  destroyed  through  a  peculiar  procedure 
which  seems  to  be  different  from  the  means  employed  in  other  parts 
of  the  organism,  but  which  is  not  yet  well  understood.  These  modi- 
fications are  slowly  effected.  Xot  infrequently,  therefore,  the  germs 
may  persist  for  a  long  period  of  time,  this  period  varying  with  the 

1  Perez.  Modo  di  comportarsi  del  sistema  ganglionare  linfatico  rispetto  ai  microor- 
gamsmi,     Labori  di  Laboratories  publicati  dal  L.  Manfredi.  Palermo.  1S97.  vol.  iii. 


384  IXFECTIO  US  DISEASES. 

microbe  and  the  animal  employed  in  the  experiment.  For  instance, 
the  staphylococcus  aureus  survives  forty  days  in  the  guinea-pig  and 
thirty  days  in  the  dog.  It  is  interesting  to  note  that  all  other  parts 
of  the  organism  no  longer  contain  any  microbes,  while  some  are  still 
present  in  the  lymphatic  glands.  This  persistence  of  germs  explains 
certain  relapses,  notably  those  of  eiysipelas.  I  believe  the  same 
fact  accounts  for  the  morbid  incidents  occurring  during  convales- 
cence from  scarlatina.  The  anginous  lesions  which  characterize 
the  onset  of  this  infection  permit  the  penetration  of  the  buccal 
streptococcus  into  the  lymphatic  network;  the  cervical  glands  are 
congested.  Later,  at  the  moment  of  convalescence,  a  new  infection 
of  ganglionic  origin  may  occur;  then  the  patient  has  fever  and 
complains  of  painful  adenopathia.  In  some  cases  the  ganglionic 
infection  remains  uncomplicated;  in  other  instances  it  is  followed 
by  more  or  less  serious  events,  and  notably  an  attack  of  nephritis. 

The  lymphatic  glands,  like  all  the  dependencies  of  the  lymphatic 
system,  are  especially  developed  during  childhood.  In  fact,  it  is 
at  this  period  of  life  that  the  danger  of  infection  is  greatest.  The 
Emphatic  system  is,  therefore,  most  vigilant  and  enjoys  its  greatest 
functional  energy.  The  slightest  lesion  causes  ganglionic  congestion. 
When  an  agent  is  highly  pathogenic  it  freely  traverses  the  lymphatic 
system  and  produces  a  general  infection  without  the  development 
of  any  adenopathy.  The  latter  manifestation  is  likewise  wanting 
or  remains  unnoticed  when  the  agent  is  but  slightly  virulent,  It  is 
in  infections  of  medium  intensity,  therefore,  that  the  ganglionic 
phenomena  must  be  studied.  The  development  of  adenopathies 
depends  upon  two  factors:  the  nature  of  the  pathogenic  agent  and 
the  state  of  the  individual.  With  individuals  whose  organisms  are 
incapable  of  energetic  reaction,  adenopathy  is  little  marked;  it  is 
insufficient.  In  the  contrary  case,  especially  in  children,  it  is  too 
energetic  and  expressed  by  lesions  which  survive  the  cause,  and  may 
give  rise  to  numerous  incidents  during  and  after  the  infectious 
process;  such,  for  instance,  is  the  case  in  tracheobronchial  adenop- 
athies compressing  the  respiratory  passages  and  the  nerves  of  the 
neighborhoods. 

Histological  Study.  The  presence  of  bacteria  causes  in  the 
lymphatic  glands  modifications  well  studied  by  Drs.  Bezancon  and 
Labbe,  who  have  made  numerous  experiments  on  this  subject. 
The  effects  vary  according  to  the  activity  of  toxins.  If  the  latter 
are  of  medium  energy,  reactionary  phenomena  are  produced.     If 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM. 

they  are  extremely  energetic,  necro  i  occui  ,&\  times  with  astonish- 
ing rapidity.  In  fifty  minutes  the  diphtheritic  toxin  gives  rise  to 
cellular  degenerations  and  fibrinoid  exudate  .  It  a  little  serum  be 
injected  at  the  same  time  or  I  wenty-four  hours  previou  ly,  reaction- 
ary phenomena  appear  (Bezancon  and  Labbe  , 

The  reactionary  phenomena  are  grouped  under  three  division 
congestion,  proliferation  of  the  fixed  cells,  and  arrival  of  polynuclear 
cells. 

Congestion  is  at  limes  so  intense  as  to  provoke  hemorrhage.  Such 
is  the  ease,  particularly,  in  pneumonia,  anthrax,  and  diphtheria. 
The  fixed  and  endothelial  cells  sunn  become  swollen  and  form  macro- 
phages, which    mingle  with    the    leucocytes,    while   the    lympIlOC 

continue  to  multiply  in  the  follicles  by  karyokinesis.  At  the  same 
time  the  polynuclear  cells  arrive.  It  is  known  thai  the  gland  con- 
tains normally  no  other  than  polynuclear  cells  and  lymphocytes. 
The  polynuclears  arrive  through  the  afferent  lymphatics  vessel  and 
the  bloodvessels — i.  c,  the  capillaries.  This  leucocytosis  occurs 
early;  it  appears  three-quarters  of  an  hour  after  bacterial  inoculation. 
then  it  increases  progressively,  to  again  decline  toward  the  eighteenth 
hour.  Those  modifications  are  especially  marked  in  the  gland- 
corresponding  to  the  invaded  point,  but  also  occur  with  the  same 
characters  in  distant  glands,  only  with  less  intensity. 

Beside  these  defensive  reactions  we  must  note  the  necrotic  pro« 
The  cells  undergo  hyaline  degeneration,  especially  in  slow  c 
The  dilated  lymphatic  channels  are  filled  with  pale,  large  cells  with 
a  vitreous  protoplasm  and  a  colorless  nucleus.     The   polynuc 
leucocytes  that  have  migrated  into  the  glands  are  also  involve.!, 
though  in  a  different  manner;  their  nucleus  is  fragmented  and  r<  - 
duced  to  fine  granules.     The  follicular  system,  the  most  resisting 
part,  also  finally  undergoes  degeneration,  notably  in  diphtheria. 
Lastly,  the  bloodvessels  undergo  arteritis  and  hyaline  degeneration, 
and  their  lumina  may  become  obliterated  by  thrombosis 

The  inflamed  gland  may  gradually  recover  its  normal  condition  or 
remain  enlarged.  In  the  latter  case  it  occasionally  assumes  the 
appearance  of  a  tubercular  lesion,  but  seems  to  be  due  to  the  persist- 
ence of  pyogenic  cocci.  In  other  instances  the  process  procee  - 
suppuration.  All  parts  of  the  gland  are  not  invade*  1  simultaneously : 
the  follicular  system  resists  for  a  long  time. 

Finally,  the  diseased  cells  may  not  be  replaced,  and  then  the 
inflammatory  lesion  terminates  in  sclerosis. 

25 


386  ISFECTIO  US  DISEA SES. 

Adenopathies  in  Variola.  We  cannot  review  all  the  infections 
which  affect  the  lymphatic  glands.  We  must,  however,  direct  the 
attention  of  the  reader  to  variola,  which,  from  the  standpoint  under 
consideration,  is  extremely  important,  and  which  has  hitherto  been 
overlooked.  The  only  work  on  this  subject  is  Lelandxis'  thesis, 
inspired  by  Enipis.  The  frequency  of  ganglionic  hypertrophy  in 
variola  has  been  pointed  out  by  this  author,  who  considers  it  an 
element  of  favorable  prognosis. 

The  investigations  which  were  pursued  with  Dr.  Weil  during  the 
late  variola  epidemic  in  Paris  showed  us  that  enlargement  of  the 
lymphatic  glands  is  subject  to  the  same  rules  as  hypertrophy  of  the 
spleen.  It  is  very  marked  in  pustular  types  of  smallpox,  very 
slight  or  nil  in  hemorrhagic  types.  The  enlarged  glands  are  gener- 
ally painless,  and  hypertrophy  is  apparent  from  the  beginning  of 
the  disease,  increases  during  the  period  of  eruption,  persists  during 
suppuration,  and  then  declines  and  disappears.  The  axillary  and 
inguinal  groups  are  most  frequently  involved,  although  the  topog- 
raphy of  the  exanthema  does  not  explain  this  localization. 

The  histological  features  peculiar  to  variolar  adenopathy  are  the 
presence  in  the  lymphatic  vessels  and  around  the  follicles  of  cellular 
forms  similar  to  those  found  in  the  bone-marrow,  notably  neutrophilic 
myelocytes,  a  few  basophilic  myelocytes,  and,  in  some  instances, 
eosinophilic  myelocytes.  Finally,  a  few  giant  cells,  and,  in  hemor- 
rhagic types,  nucleated  red  corpuscles  may  also  be  encountered. 
This  peculiar  evolution  (which  had  hitherto  been  observed  only  in 
leukemia)  may  extend  to  the  cellular  tissue  surrounding  the  glands. 
In  sections  its  appearance  is  similar  to  that  of  the  bone-marrow. 
The  latter  fact  further  emphasizes  the  analogy  of  the  process  to 
that  which  occurs  in  leukemia.  It  may,  therefore,  be  assumed  that 
the  cellular  tissue  itself  acquires  a  cytogenetic  activity,  and  that, 
like  the  spleen,  the  glands,  and  the  bone-marrow,  it  produces  vari- 
ous leucocytes.  This  process  has  not  thus  far  been  observed  in  any 
other  infection  than  variola.  It  would  be  interesting  to  take  up  the 
question  from  a  general  standpoint  and  investigate  the  state  of  the 
connective  tissue  in  all  infections.  I  am  convinced  that  very  pro- 
nounced modifications  will  be  observed. 

Syphilitic  and  Tubercular  Adenopathies.  Chronic  infections 
often  give  rise  to  ganglionic  lesions.  Syphilis  is  a  familiar  illustra- 
tion. The  chancre  produces  enlargement  in  a  group  of  lymphatic 
glands  among  which  one  becomes  remarkable  for  its  size.     This 


INFLUENCE  OF  INFECTIONS  UPO&  THE  ORGANISM. 

adenopathy  is  lacking  only  in  exceptional  and  g<  nerally  vi 
cases.  During  the  secondary  period  multiple  adenopathies  occur 
and  are  of  considerable  semiological  importance.  They  often  coin- 
cide wifh  hypertrophy  of  other  parts  of  the  lymphatic  system, 
especially  in  women,  whose  tonsils  and  3pleene  become  lil  • 
enlarged.  During  the  tertiary  period  germs  may  be  found  in  them, 
these  germs  presenting  no  particular  character  of  evolution. 

Tubercular  adenopathies  may  be  generalized.  This  condition  U 
mainly  observed  in  young  children.  Micropolyadenitis  ie  strongly 
suggestive  of  tuberculosis  and  more  readily  detected  than  hyper- 
trophic conditions  of  the  liver  and  spleen.  This  peculiar  evolution 
is  comparable  to  whal  is  observed  in  laboratories.  Tuberculosis 
caused  by  inoculation  into  guinea-pigs  behaves  in  exactly  the  same 
manner.  It  is  first  expressed  by  tumefaction  of  the  glands  corre- 
sponding to  the  infected  point,  and  then  all  the  glands  of  the  economy 
are  gradually  involved,  and  finally  the  abdominal  viscera.  In  some 
cases  the  thoracic  organs  also  are  affected.  The  lymphatic  system 
is  thus  seen  to  he  well  designed  to  arrest  the  course  of  invading 
bacteria,  although  in  some  rare  instances  it  may  aid  in  their  spread, 
as  is  shown  by  the  investigations  of  Ponflck  on  the  thoracic  duct. 

It  is  interesting  to  remark  that  actinomycosis,  a  disease  so  closely 
allied  to  tuberculosis,  does  not  affect  the  lymphatic  glands. 

Humoral  Modifications  of  Lymphatic  Origin.  It  is  not  merely  by 
phagocytic  action  that  the  lymphatic  glands  protect  the  system. 
It  seems  to  be  demonstrated  that  these  small  organs  secrete  germi- 
cidal and  antitoxic  substances.  The  investigations  of  Pfeiffer  and 
Marx  show  that,  during  the  immunization  of  animals,  these  glands 
produce  antitoxins  which  are  carried  into  the  circulation.  It  is  con- 
ceivable that  the  glands  of  infected  or  vaccinated  animals  may  be 
utilized  in  the  treatment  of  certain  diseases.  Manfredi  has  ma<  le  some 
attempts  in  this  direction  and  found  that  the  ganglionic  juice  of  tuber- 
culous goats  hindered  the  development  of  this  disease  in  guinea-pigs. 

The  Thymus  in  Infection. 

Anatomical  and  Physiological  Considerations.  In  its  histo- 
logical structure  the  thymus  resembles  the  lymphatic  glands.  It 
differs  from  them  in  its  embryogenic  origin.1     The  thymus  has  at 

1  Ghika.  Etude  sur  le  thymus.  These  de  Pari.-?.  July.  1901.  This  is  a  very  complete 
monograph  containing  a  great  number  of  histological  and  experimental  researches  pur- 
sued in  our  laboratory. 


388  IXFECTIOUS  DISEASES. 

first  an  epithelial  structure;  later  it  assumes  a  lymphoid  character 
as  a  result  of  direct  transformation  of  the  primary  elements.  We 
found  this  transformation  completed  in  a  fetus  of  three  months. 
In  the  fetus  of  six  months  appear  peculiar  formations — the  corpuscles 
of  Hassall — the  aspect  of  which  is  absolutely  characteristic.  From 
the  sixth  month  onward  and  until  the  period  when  regression  sets 
in  the  thymus  undergoes  no  appreciable  modification  in  structure. 
The  cells  contained  in  the  fibrillary  network  are  mostly  lymphocytes ; 
besides  these  there  are  also  some  neutrophilic  and  fewer  eosinophilic 


Fig.  26. 


Normal  cat,  one  month.  Reticulum  quite  visible.  Numerous  lymphocytes.  Tra- 
becular cells  with  large  clear  nucleus  and  distinct  nucleolus.  Large  corpuscles  of  Hassall. 
Epithelioid  fragments  in  the  centre.     Numerous  vessles  filled  with  blood  corpuscles. 


polynuclears,  non-granular  mononuclears,  mastzellen,  granular  mono- 
nuclears or  eosinophile,  basophile,  or  neutrophile  myelocytes,  rarely 
giant  cells,  and  elements  resembling  nucleated  red  globules.  Finally, 
there  are  also  epithelioid  cells  and  large  cells  with  vesicular  nucleus. 
Hassall's  corpuscles  have  an  extremely  variable  appearance.  They 
are  occasionally  formed  by  a  single  enormous  cell;  the  chromatin 
of  the  nucleus  presents  the  most  varied  figures. 


INFLUENCE  OF  TNFE0TI0N8  UPON  THE  ORGANISM. 

The  thymus  grows  smaller  with  age.     W  i     oon  invaded  b 
profuse  cellulo-adipose  ma   ,  bu1   doe    no1   completely  disappear, 
The  corpuscles  persist  for  a  long  time,  but  di  appear  in  the  very  aged. 

In  animals  this  gland  present  a  structure  very  much  similar  to 
the  human.  The  same  cellular  form  are  found;  the  only  essential 
difference  is  in  the  number  and  appearance  of  Hassall's  corpuscles. 
In  the  rabbit,  guinea-pig,  and  ral  these  corpuscles  are  extremely 
rare,  and  are  composed  mostly  of  a  3ingle  large  cell.  The  cat,  on 
the  contrary,  has  very  clear  corpuscles,  and  while  it  is  alwaj 
differentiate  in  sections  a  thymus  of  a  child  from  thai  of  a  rabbit, 
guinea-pig,  or  rat,  it  is  almosl  impossible  to  distinguish  the  human 
thymus  from  that  of  a  cat.  In  frogs  and  hibernating  animals  the 
thymus  is  voluminous  in  the  summer  and  small  in  winter.  Path- 
ology teaches  us  thai  this  gland,  which  is  highly  developed  in  well- 
nourished  children,  atrophies  in  feeble  or  cachectic  children.  I-  the 
atrophy  the  cause  or  the  effecl  of  the  nutritional  disorders? 

To  solve  this  problem  experimentation  should  be  resorted  to.  A 
great  many  times,  therefore,  the  gland  has  been  extirpated.  On 
the  other  hand,  attempts  have  been  made  to  aso  rtain  the  efifec 
injection,  ingestion,  and  inoculat  ion  of  extract.-  of  this  gland.  With- 
out wishing-  to  dwell  upon  the  details  of  the  experiment-  related  in 
the  thesis  of  Dr.  Ghika,  we  believe  thai  facts  warrant  us  in  con- 
cluding that  the  thymus  plays  an  important  parr  in  nutrition.  In 
order  to  obtain  clear  evidence  very  young  animals  musl  be  operated 
upon.  Our  best  experiment  was  made  upon  a  cat  fifteen  days  old. 
The  extirpation  of  the  thymus  was  complete.  The  animal,  which 
weighed  485  grams,  increased  in  weight  to  635  grams  in  twenty- 
two  days.  An  animal  of  the  same  litter,  kept  as  control,  weighed 
then  890  grams.  From  this  moment  onward  the  operated  one 
began  to  lose  flesh.  At  the  end.  of  thirty-five  days  it  succumbed 
in  a  state  of  profound  cachexia.  It  then  weighed  430  grams,  55 
grams  less  than  at  the  beginning  of  the  experiment,  while  the  weight 
of  the  control  reached  1090  grams. 

Among  the  symptoms  observed  in  animals  in  which  the  thymus 
is  extirpated  we  may  mention,  besides  emaciation,  arrest  of  growth, 
anomalies  of  the  skeleton,  especially  costal  deformities,  trembling, 
stupor,  weakness,  and.  in  some  cases,  paralysis.  These  various 
manifestations  may  be  slight  or  absent  as  the  result  of  supplemental 
activity  on  the  part  of  other  hematopoietic  organs,  at  least  in  certain 
cases.     At  the  necropsy  of  the  animals  experimented  on  we   found 


390  IXFECTIOUS  DISEASES. 

the   bone-marrow   red   and   proliferated;   histological   examination 
demonstrated  its  vicarious  activity. 

Besides  being  a  gland  with  an  internal  secretion  the  thymus  has 
an  important  cytopoietic  function.  Its  structure,  being  similar  to 
that  of  all  adenoid  tissues,  leads  to  the  conclusion  that  it  forms 
white  blood  corpuscles.  The  experiments  pursued  on  this  question 
have  not  given  very  clear  results,  probably  because  other  hemato- 
poietic organs  rapidly  come  into  play  and  prevent  the  development 
of  manifestations. 

Histological  Modifications  of  the  Thymus  in  Infections.  The 
histological  study  of  the  thymus  leads  to  clearer  conclusions.  In  a 
great  variety  of  physiological  or  pathological  circumstances  cellular 
proliferations  entirely  comparable  to  those  occurring  in  the  bone- 
marrow  are  observed. 

Cellular  proliferation  takes  place  in  inanition,  intoxications,  and 
infections.  We  have  been  able  to  study  these  in  animals  intoxicated 
by  phosphorus  or  carbonic  oxide  as  well  as  in  those  inoculated  with 
the  most  varied  microbes  or  poisoned  by  the  toxin  of  diphtheria, 
We  have  found  the  same  modifications  in  the  thymus  glands  of 
children  dead  from  variola,  measles,  erysipelas,  whooping-cough, 
syphilis,  and  tuberculosis. 

This  study  of  modifications  of  the  thymus  in  infections  is  entirely 
new.1  The  only  information  found  in  authoritative  works  consists 
of  a  fewr  macroscopic  examinations.  From  these  it  might  be  inferred 
that  the  thymus  does  not  react  in  infections  or  that  it  occasionally 
undergoes  partial  degenerations.  This  opinion  does  not  seem  to  us 
acceptable.  The  thymus  is  constantly  modified  in  the  course  of 
various  infectious  processes.  It  may  be  seen  with  the  naked  eye 
that  the  gland  is  enlarged,  red,  and  congested.  It  may  even  be  the 
seat  of  hemorrhages.  In  other  instances  it  may  be  pale  and  anemic. 
Under  the  microscope  modifications  in  the  fibrillary  network,  vessels, 
cells,  and  Hassall's  corpuscles  can  be  seen.  The  fibrillary  substance 
is  only  slightly  affected,  at  least  when  the  process  is  acute.  In 
some  cases  it  becomes  thickened.  The  bloodvessels  are  congested, 
and  their  walls  are  often  infiltrated  with  yellow  cells.  At  certain 
points  thromboses  and  hemorrhages  are  observed.  The  principal 
modifications  are  found  in  the  cellular  elements.     The  lymphocytes 

1  Roger  and  Ghika.  Recherches  sur  l'anatomie  normale  et  pathologique  du  thymus, 
XHIe  Congres  intern,  de  m^decine,  section  de  pathologie  generate,  p.  219.  Journal  de 
phys.  et  pathol.  generate,  Sept.,  1900. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      301 

and  the  small  mononuclears  alwayi  form  the  fundamental  pari  of 
the  gland.  Bui  a  greater  number  of  large  mononucleai  inter- 
mediate forms,  and  polyneutrophilei  are  me1  with.  The  poly- 
eosinophiles  and  nucleated  i*< ** I  globulei  are  •,il"  more  numerous. 
Moreover,  there  appear  elements  which  are  either  absenl  or  rare  in 
the  normal  thymus— mastzellen,  myelocytes,  leucocytes  with  mixed 
granulations,  and,  in  animals,  pseudoeosinophiles.  There  are  also 
encountered  two  special  varieties  of  non-granular  mononuclears. 
Some  are  large  cells  measuring  from  \~>,"  to  -"//,  with  volumin- 

l  i...  27. 


Child  of    two  months,  dead  from  erysipelas  of    the  face.      Rei 
dating  the  lymphocytes.       Numerous    granular  forms.       Cystic    Hassall's 
with  colloid  contents  in  the  form  of  onion  bulbs,   unicellular  or  paucicellular. 

ous  excentric  nucleus;  the  protoplasm  stains  strongly  with  thionin. 
but  faintly,  if  at  all,  with  eosin.  The  others  are  equally  large  cells 
with  a  dark  protoplasm  and  hardly  visible  nuclei.  The  former 
resemble  plasma  cells,  the  latter  the  irritation  cells  of  Tiirck. 

Besides  these  functional  modifications,  lesions  also  occur.  The 
cells  may  undergo  granular,  vacuolar,  or  fatty  degeneration,  coagula- 
tion necrosis,  and  karyolysis.  At  times  necrotic  foci  are  formed  in 
which  all  the  elements  are  destroyed. 


392  IXFECTIO  US  DISEASES. 

All  infections  do  not  act  with  the  same  intensity,  but  all  do  act. 

Erysipelas  is  one  of  the  diseases  the  action  of  which  is  most 
marked.  The  thymus  is  remarkable  for  the  development  of  numer- 
ous granular  myelocytes. 

Histological  examination  of  a  certain  number  of  thymus  glands 
always  reveals  the  existence  of  sclerotic  lesions  in  some  of  them. 
Ghika  examined  sixty-four  glands,  and  found  sixteen  of  them 
sclerosed.     In  eleven  of  the  cases  the  lesions  were  very  pronounced. 


Fig.  2S. 


■■  ■  \Vs^>&   'v  \5— r  :>    "-■■$.'■*,  "  ■  '.-''."'V 


* 


The  same  preparation  as  in  the  preceding  figure,  more  highly  magnified.  Very  large 
corpuscles  of  Hassall,  containing  cells,  cell  fragments,  and  colloid  substance.  The  wall 
is  formed  of  epithelioid  cells,  which  are  clearly  continued  on  the  right  side  with  the 
trabecular  cells.  In  the  left  lower  corner  is  seen  a  large  cell  composed  of  a  clear  nucleus 
and  rounded  protoplasm,  containing  fine  eosinophile  granulations  disposed  in  concen- 
tric circles. 

These  sclerotic  lesions  of  the  thymus  are  occasionally  observed 
in  children  dead  of  acute  diseases.  In  such  instances  it  is  quite 
certain  that  the  lesions  existed  previous  to  the  occurrence  of  the 
acute  malady.  They  sometimes  depend  upon  involution  of  the 
gland.  When,  however,  the  lesions  are  found  in  young  children 
they  must  be  attributed  to  s3Tphilis  or  some  antecedent  infection, 
to  bad  hygiene,  athrepsy,  or  some  hereditary  taint.    Syphilis,  tuber- 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM. 

culosis,  alcoholism,  and  defective  nutrition  of  the  parenl    are  the 
most  frequent  causes. 

Primary  Infection  of  the   Thymus.     Although    the   thymu 
almost  invariably  affected  in  the  course  of  infectious  di  ea  e  .  il  U 
seldom  the  seal  of  a  primary  affection.    There  are  bul  few  facte 

013  record. 

VV.  Wittich  has  reported  the  case  of  a  young  man,  aged  eighteen 
years,  who  was  suddenly  seized  with  dyspnea  and  retrosternal  pain, 
and  who  was  soon  attacked  by  hydrothorax  and  ascites.  He  suc- 
cumbed to  a  paroxysm  of  dyspnea.  The  autopsy  revealed  an  enor- 
mous thymus  filled  with  purulenl  cavities.  The  pericardium 
healthy.  Demnie  published  a  similar  case.  In  a  child  of  two  and 
a  half  months  was  found  a  purulenl  transformation  of  the  thymus, 
which  was  manifested  during  life  by  a  red  and  painful  tumor  occupy- 
ing the  lower  pari  of  the  neck.  Schlossmann,  Helm,  and  Biederl 
have  recorded  cases  of  rapid  death  preceded  by  paroxysms  of  suffo- 
cation iii  young  children.  The  necropsy  showed  a  voluminous, 
inflamed  thymus  (Biedert),  or  one  infiltrated  with  pus.  In  Schloss- 
mann's case  bacteriological  examination  revealed  a  microbe  anal- 
ogous to  Fischer's  pyobacterium.  Demme  has  related  an  incon- 
testable case  of  primary  tuberculosis  of  the  thymus  in  a  little  girl. 
Syphilitic  gummata  and  sclerosis  may  develop  in  this  gland  as  well 
as  in  any  other  organ. 

The  Thyroid  Gland  in  Infectious  Diseases. 

The  only  lesion  of  the  thyroid  that  has  been  described  in  infections 
is  suppurative  thyroiditis.  This  involvement  is  so  rare  that,  if  it 
was  the  only  one  that  may  occur,  the  participation  of  this  gland  in 
infectious  processes  should  be  regarded  as  exceptional.  Systematic 
examination  of  the  thyroid  in  all  the  necropsies  which  we  made 
during  one  year  led  us  to  a  different  opinion.  Far  from  being 
indifferent  in  the  presence  of  infection,  this  gland  always  reacts 
more  or  less  energetically,  and  this  reaction  is  expressed  by  histo- 
logical modifications  which  we  have  studied  with  Dr.  Gamier.1  Let 
us  first  briefly  consider  certain  details  of  normal  histology. 

1  Roger  and  Gamier.     Infection  thvroidieime  experimentale.     Soc.  de  biol.,  Ocl 
1S0S.    Action  du  bacille  typhique  snr  la  glande  thyroide.     Ibid.     La  glande  thyroide 
dans  les  maladies  Lnfectieuses.     Presse  medicate,  April  19,   1899.     Recherches  experi- 
mentales  sur  les  infections  thyroidiennes.     Ibid..  August  9,  1900. 


394  INFECTIOUS  DISEASES. 

Remarks  on  Normal  Histology.  The  thyroid  apparatus  is  com- 
posed in  man,  as  in  other  mammals,  of  two  distinct  parts — the 
thyroid  gland  proper,  described  in  all  classical  treatises,  and  the 
parathyroids — small  glands  discovered  by  Sandstrom  in  1880,  the 
physiological  importance  of  which  was  proved  by  Gley  in  1892. 

The  structure  of  the  thyroid  is  not  the  same  in  the  adult  and  in 
children.     Defaucamberge  was  the  first  to  show  this  difference  in 

Fig.  20. 


' c  ^' 


V 


3 


Thyroid  gland  in  children.  This  figure  and  the  following  three  are  taken  from  the 
work  which  we  published  with  Dr.  Garnier  (La  glande  thyroide  dans  les  maladies 
infectieuses),  Presse  mddicale,  April  19,  1S99. 

1889,  and  distinguished  two  types:  the  truly  glandular  type,  which 
is  found  in  the  child  and  is  more  or  less  marked  until  puberty,  and 
the  colloid  type,  which  corresponds  to  the  normal  state  in  adults. 
The  thyroid  gland  in  children  is  formed  of  distinct  lobules,  separated 
from  each  other  by  connective  tissue.     (Fig.  29.) 

This  tissue  enters  the  lobules  and  divides  them  into  smaller  depart- 
ments, each  of  these  containing  two  or  three  vesicles.  The  connective 


INFLUENCE  OF  INFECTIONS  UPON  TEE  ORGANISM, 

tissue  contains  numerous  nuclei  and  an  abundanl  ba  emenl  sub- 
stance. Each  vesicle  i.  lined  bya  layer  of  lowly  organized  cella;  the 
centre  is  occupied  by  colloid  iri.it  ter. 

In  the  thyroid  gland  of  the  adull  the  mosl  Btriking  feature  us  the 
complete  absence  of  the  lobulated  tructure.  (Fig.  30.)  The  nol 
abundant  connective  (issue  is  reduced  to  fine  trabecular  running 
between  the  vesicles.    The  glandular  parenchyma  appears  to  be 


)■    :::■■- 


t.K  i 


I  i..   30 

..■;/ 


..-/,:.--.• 


Thyroid  gland  of  a  normal  adult. 

formed  simply  by  juxtaposition  of  closely  arranged  colloid  mass  ~. 
or  is  separated  here  and  there  by  a  cellular  mass. 

The  parathyroids  are  small  organs  situated  in  the  neighborhood 
of  the  thyroid,  but  differing  from  it  in  origin  and  structure.  They 
are  chiefly  met  with  near  the  point  at  which  the  thyroid  arteries 
enter  the  gland.  The}-  vary  in  number  and  size.  They  do  not 
present  the  vesicular  arrangement  or  the  colloid  substance  of  the 
thyroid.     They  are  surrounded  by  a  capsule  of  connective  tissue 


396 


INFECTIOUS  DISEASES. 


covering  the  whole  gland  and  extending  into  its  interior  partitions, 
which  divide  it  into  irregular  departments.  The  meshes  thus 
formed  are  filled  with  rows  of  cubical  epithelial  cells  with  well- 
stained  nuclei  and  surrounded  by  a  profuse  granular  protoplasm. 
These  cells  are  pressed  one  against  the  other  and  exactly  applied 
on  the  one  hand  to  the  connective  tissue  wall  and,  on  the  other,  to 
the  neighboring  row. 

Fig.  31. 


*  m* 


;S  «■*  £* 


&■>$%&*■ 


;'-%' 


Thyroid  gland  of   a  man   dead  from  scarlatina.     Considerable    dilatation    of   vessels. 
Trains  of  colloid  matter   surrounding  the  vesicles. 


General  Characters  of  the  Thyroid  in  Acute  Infections.  When 
examined  with  the  naked  eye  the  gland  appears  enlarged.  While 
normal^  its  weight  is  about  25  grams  (1  ounce),  we  found  it  in 
seven  cases  to  reach  from  37  to  71  grams  (1£  to  2\  ounces).  The 
color  is  changed  from  its  normal  hue — that  is,  yellowish — into  red, 
sometimes  blue.  The  connective  tissue  is  only  slightly  modified 
and  usually  undergoes  no  pronounced  alteration.     At  times,' how- 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      397 

ever,  especially  in  children,  il  eem  bo  contain  a  greater  number  ol 
nuclei  than  normal.  The  pre  ence  of  colloid  lib  tance  oul  ide  the 
vesicles  changes  the  general  appearance  of  the  gland  and  may  lead 
to  the  belief  thai  the  connective  ti  uei  hypertrophied.  (Fig.  31  , 
This  colloid  substance  dilates  the  lymphatic  pacef  of  the  gland  and 
produces  a  more  or  less  complete  network,  the  mesne*  of  which  are 
filled  with  vesicles.  The  vessels  are  dilated.  There  is  ometimes 
arteritis  and  phlebitis.    The  inflammation  of  the  vessels,  howi 

Ik;.  32. 


v          :■  -  ■ 

•; 

. 

•V-^v  » ...  \  •    - 

'       -};v,      !  v' - 

_                     • 

Thyroid  gland  of  an  adult  dead  from  scarlatina.  Lobule  completely  transformed; 
the  vesicles  contracted  and  crowded  with  cells;  the  thyroideal  tissue  is  still  recognizable 
by  a  few  dilated  vesicles  at  the  border  of  the  lobule;  the  colloid  substance  no  longer 
takes  eosin. 

presents  nothing  particular.  The  vesicles  are  commonly  smaller 
than  normal.  Their  composition  is  often  profoundly  modified:  some 
of  them  no  longer  contain  any  colloid  substance,  and  their  centre  is 
occupied  only  by  cells  in  course  of  degeneration.  In  many  cases 
the  protoplasm  of  several  cells  at  the  centre  of  the  vesicle  is  fused 
in  a  finely  granular  mass  in  the  midst  of  which  are  seen  degenerated 
nuclei.  On  the  other  hand,  some  vesicles  still  contain  a  certain 
quantity  of  normal  colloid  substance  in  the  midst  of  desquamated 


398  IXFECTIO  US  DISEASES. 

cells.  When  the  lesions  are  very  marked  (Fig.  32)  the  secretion  of 
the  colloid  matter  seems  to  be  hindered  or  replaced  by  a  few  granu- 
lations. 

We  have  histologically  examined  the  parathyroids  in  three  cases 
of  scarlatina  and  in  one  case  of  diphtheria.  Only  in  two  of  the 
casi  is  were  they  found  to  be  altered.  The  most  important  alterations 
were  observed  in  the  case  of  a  woman  who  died  from  scarlatina. 
While  the  thyroid  had  deviated  but  little  from  the  normal  type,  the 
glandules,  four  in  number,  presented  interesting  modifications.  The 
connective  meshes  were  half  empty;  the  cells  had  lost  the  arrange- 
ment in  regular  rows  and  were  found  in  masses  at  the  centre  of  each 
mesh.  They  were  often  formed  by  granular  protoplasm  with  poorly 
marked  limits.  The  nucleus  stained  well.  These  lesions,  although 
diffuse  and  encountered  in  all  parts,  did  not  involve  the  entire 
gland;  on  the  contrary,  certain  portions  remained  perfectly  healthy. 

In  a  case  of  diphtheria  the  same  appearance  was  found,  but  the 
lesions  were  more  discrete. 

It  is  well  to  remark  that  the  frequency  of  thyroideal  lesions  varies 
considerably  according  to  different  infections.  In  scarlatina  the 
thyroid  is  almost  constantly  the  seat  of  profound  alterations,  while 
it  resists  far  better  in  measles.  In  the  case  of  a  woman  who  died 
from  confluent  variola  the  gland  was  the  seat  of  very  pronounced 
lesions.  It  was  hypertrophied  and  highly  congested;  small  paren- 
chymatous hemorrhages  had  also  occurred. 

Mechanism  and  Significance  of  Thyroideal  Lesions.  Torry1 
attributes  to  the  thyroid  gland  a  special  destructive  power  against 
bacteria.  This  action,  if  real,  cannot  be  considerable.  The  injec- 
tions made  through  the  carotid  vessels  are  at  least  as  effective  as 
intravenous.  On  the  other  hand,  rabbits  subjected  to  thyroid- 
ectomy resist  at  least  as  well  as  normal  rabbits.  Moreover,  under 
the  influence  of  infections  the  thyroid  is  not  spared;  it  presents 
the  same  alterations  as  the  other  parenchymatous  structures.  The 
reason  the  lesions  in  the  thyroid  are  generally  less  pronounced  than 
those  in  the  liver  and  kidney  is  that  the  activity  of  the  thyroid  is 
slow  in  the  adult.  The  first  effect  of  infection  is  to  arouse  the  torpid 
secretory  activity ;  for  profounder  changes  to  be  effected  the  action 
of  the  toxic  product  must  be  intense  or  long  continued. 

1  Torry.  La  tiroide  nei  morbi  infettivi.  II  policlinico,  March  15,  April  15,  and 
May  15,  1900. 


INFLUENCE  OF  INFECTIONS  UPOJS    THE  0RQANI8M. 

In  this  connection  experiment  demon  trate  thai  chronic  ii 
<  ions  give  rise  in  mosl  cases  to  interstitial  le  ion  ;  inter  e  infections, 
even  when  of  shori  duration,  produce  chiefly  cellular  alterations. 
II.  may,  therefore,  be  concluded  thai  the  extenl  and  depth  of  le 
depend  rather  upon  the  energy  than  upon  the  persistence  of  the 
morbid  processes.  This  l;iw  of  general  pathology  is  clearly  demon- 
strated by  experimental  facts  obtained  by  us.  By  injection  of 
microbes  into  the  thyroideal  arteries  we  have  been  able  to  produce 
nil  degrees  of  visceral  inflammation.  By  varying  the  dose  or  the 
virulence  of  cult urcs  one  may  obtain  thyroiditis  with  interstitial 
predominance—  /.  e.,  hemorrhagic  thyroiditis,  thyroiditis  with  active 
leucocytic  reaction  :ind  sclerosis,  or  thyroiditis  with  parenchymatous 
predominance,  namely,  acute  necrosis  and  degeneration  of  the  cells, 
or  even  epithelial  proliferation  terminating  in  neoplastic  develop- 
ment. 

These  experimental  data  arc  interesl  ing,  since  the  same  anatomico- 
pathological  types  may  occur  in  man.  Suppurative  thyroiditis, 
which  has  long  been  noted,  is  to-day  well  known:  it  develops  in 
the  decline  of  various  infectious  diseases.  Bemorrhagic  thyroiditis 
is  rare;  it  has  been  observed  in  variola  by  Liouville  and  ourselves. 
The  other  forms  may  be  encountered  in  acute  infection-,  though 
they  never  present  the  intensity  observed  in  experimental  inflam- 
mations. Thyroideal  sclerosis  is  rather  an  incident  of  chronic  dis- 
eases, such  as  tuberculosis.  It  may,  however,  appear  in  the  course 
of  the  most  varied  infections  when  these  are  more  or  less  prolonged. 

How  are  the  various  parenchymatous  modifications  of  the  thyroid 
to  be  interpreted?  Experimental  pathology  enables  us  to  answer 
this  question.  If  the  infected  thyroid  lie  compared  to  glands  the 
activity  of  which  is  excited  by  pilocarpine  or  iodine,  the  phenomena 
are  found  to  be  practically  the  same.  Infection  arouses  the  gland- 
ular activity,  which  is  expressed  by  increased  secretion.  This  is  the 
first  degree.  "When  the  process  is  more  intense  the  colloid  matter 
suffers  qualitative  modifications.  Unlike  what  occurs  in  animals 
treated  with  pilocarpine  or  iodine,  it  undergoes  a  granular  trans- 
formation and  loses  its  normal  staining  capacity.  Thus  in  the  course 
of  infectious  diseases  more  or  less  marked  secretory  disorders  in  the 
thyroid,  as  in  other  glands  of  the  economy,  occur.  After  a  period 
of  overactivity  a  diminution  or  an  alteration  oi  functions  appears. 
As  the  liver  then  secretes  abnormal  pigments,  so  the  thyroid  forms 
an  atypical  and  peculiar  colloid  substance. 


400  IXFECTIOUS  DISEASES. 

Although  in  the  majority  of  cases  the  thyroideal  lesions  are  slight 
and  admit  of  sufficient  reparation  to  permit  the  re-establishment 
of  its  functions,  it  is  clear  that  such  may  not  always  be  the  case. 
Alterations  may  subsist  which,  at  the  end  of  a  variable  period  of 
time,  perhaps  several  years,  having  evolved  on  their  own  account, 
may  be  expressed  by  functional  disturbances;  for  instance,  myx- 
edema and  exophthalmic  goitre  may  be  connected  with  some 
previous  infection. 

The  Suprarenal  Capsules  in  Infectious  Diseases. 

The  suprarenal  capsules  may  be  altered  in  the  course  of  the  most 
varied  infections. 

Capsular  alterations  are  very  frequent  in  syphilis  (Virchow,  Lan- 
cereaux,  Chvostek)  and  especially  in  hereditary  syphilis.  Virchow 
and  Huber  noted  fatty  degeneration  in  them.  Boerensprung,  Ollivier 
and  Ranvier  described  sclerosis  of  the  capsules. 

Since  the  classical  memoir  of  Addison,  tuberculosis  of  the 
suprarenal  capsules  has  been  described  a  great  many  times. 
There  may  also  be  cited  cases  in  which  the  capsular  lesions  seem 
to  have  played  the  principal  role  in  the  genesis  of  morbid  phe- 
nomena. In  two  patients  who  had  rapidly  died  with  typhoid 
symptoms  Virchow  found  a  hemorrhagic  inflammation  in  the  supra- 
renal capsules. 

These  facts  indicate  the  interest  attaching  to  the  systematic  study 
of  the  suprarenal  capsules  in  infections.  In  their  memoir  on  diph- 
theria Roux  and  Yersin  state  that  the  suprarenal  capsules  are 
intensely  congested  in  guinea-pigs  which  had  received  living  or  ster- 
ilized cultures  of  Loeffler's  bacillus.  Charrin  and  Langlois  made  anal- 
ogous statements  regarding  guinea-pigs  inoculated  with  pyocyaneus 
virus  and  noted  the  presence  of  small,  pigmentary  granulations  in 
the  interior  of  the  cells.  In  guinea-pigs  which  died  twenty-four  hours 
after  inoculation  with  Friedlaender's  bacillus  the  author  found1  the 
suprarenal  capsules  enlarged;  instead  of  the  fine  yellow  color  they 
presented  a  dark,  ecchymotic  hue.  In  some  instances  they  appear 
totally  invaded  by  hemorrhages.  On  section  the  parenchyma  ap- 
pears transformed  simply  into  a  bloody  mass;  at  the  periphery  of 
the  organ  only  some  intact  parts  are  at  times  encountered. 

1  Roger.    Les  lesions  des  capsules  surrenales  dans  les  maladies  infectieuses.    La  presse 
m<jdicale,  February  3,  1894. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       |0| 

Oppenheim  and  Loper  studied1  the  uprarenal  cap  ule  ol  fifty- 
three  men  who  had  died  from  the  mo  I  varied  infection  .  ! 
constantly  found  lesions,  dilatation  of  the  capillaries,  diffuse  or  cir- 
cumscribed hemorrhages,  venous  thromboses,  cellular  necroses,  and, 
here  ;iikI  there,  masses  of  polynuclears.  These  are  substantially  the 
same  modifications  as  those  observed  in  animal  , 

Considering  the  various  results  obtained  and  the  frequenl  occur- 
rence of  sclerosis  as  a  result  of  infectious  lesions,  we  are  led  to  the 
assumption  thai  after  an  acute  disease  the  suprarenal  capsules  often 
remain  altered  inapermanenl  manner;  therefore,  various  disorders 
due  to  their  incompetency  may  later  be  observed.  A-  a  matter  of 
fact,  since  the  clinical  investigations  of  Sergenl  and  Bernard  we 
know  that  there  is  a  syndrome  different  from  Addison's  disease,  and 
characteristic  of  capsular  insufficiency.  In  most  cases  the  symptoms 
arc  connected  with  tuberculosis  and  follow  an  acute  or  subacute 
course,  at  times  rapidly  terminating  in  death.  <  )f  special  importance 
for  our  subject  is  the  fact  that  these  phenomena  a1  times  develop 
on  the  occasion  of  even  a  slighl  infection,  such  as  a  pultaceous 
angina,  as  was  the  case  observed  by  Sergent  and  Bernard.2 

1  Oppenheimer  and  Loper.  Lesions  des  capsules  Burrenales  dans  quelques  maladi>- 
infectieuses  aigii-s.    Socictc  de  biologic,  July  13,  1901. 

7  Sergent  and  Bernard.  Sur  un  syndrome  clinique  non  addisonien  lie1  a  1  'insuffi.sance 
capsulaire.     Archives  generales  de  ni(5decine,  July,  1899. 


26 


CHAPTER    XIV. 

INFLUENCE  OF  INFECTION  UPON  VARIOUS  PARTS  OF 
THE  ORGANISM  {Continued). 

Disturbances  and  Alterations  of  the  Nervous  System.  Cerebral  Manifestations.  Ceph- 
alalgia. Delirium.  Relationship  between  Delirium  and  Lesions  of  the  Liver  and 
Kidney.  Post-infectious  Delirium.  Tubercular  Insanity.  Obnubilation  and  Coma. 
Aphasia.  Hemiplegia.  Convulsions.  Bulbar  Manifestations.  The  Spinal  Cord  in 
Infections.  Hydrophobia.  Tetanus.  Infectious  Myelitis  in  Man.  Acute  Ascend- 
ing Paralysis.  Infantile  Paralysis.  Myelites  in  Various  Infections.  Diphtheritic 
Paralyses.  Post-infectious  Neuroses.  Infectious  Meningites.  Cutaneous  Manifes- 
tations of  Infections.  Exanthemata  in  the  Eruptive  Fevers.  Mechanism  and 
Variability  of  Infectious  Erythemata.  Relationship  Between  the  Intensity  of 
Eruption  and  Gravity  of  the  Disease.  Sudoral  Secretion  in  Infections.  Evolu- 
tion of  Exanthemata.  The  Muscular  System  in  Infections.  Infectious  Osteop- 
athies and  Arthropathies. 

The  Nervous  System  in  Infections. 

All  infectious  diseases  are  capable  of  involving  the  nervous 
system;  a  few  affect  it  in  an  exclusive  or  predominant  manner. 

For  the  convenience  of  description  we  may  admit  the  following 
di  visions : 

1.  Reactionary  disturbances  of  the  nervous  system  in  the  course 
of  infections. 

2.  Non-specific  lesions  of  the  nervous  system. 

3.  Awakening  or  appearance  of  nervous  affections. 

4.  Specific  lesions,  viz.,  secondary  localization  of  the  infectious 
process. 

5.  Primary  infection  of  the  nervous  system. 

Nervous  disturbances  are  observed  in  almost  all  diseases :  fatigue, 
exhaustion,  headache,  delirium,  convulsions,  twitching  of  the  tendons, 
and  modifications  in  the  activity  of  certain  organs  or  systems  are 
manifestations  of  frequent  occurrence.  They  appear  at  a  variable 
epoch  of  the  evolution,  subside  with  it,  or  persist  after  apparent  cure 
of  the  disease.  They  may  dominate  the  morbid  tableau  by  reason 
of  their  intensity,  thus  leading  to  the  development  of  particular 
clinical  forms,  such  as  ataxic,  ataxo-adynamic,  convulsive,  delirious, 
and  comatose. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      403 

The  explanation  of  these  disturbance)  i  to  I"'  found,  il  seem  in 
intoxication. 

It,  is,  therefore,  conceivable  thai  causes  favoring  or  aggravating 
the*  formation  mid  relent  ion  of  toxic  substances  play  an  important 
role  in  (lie  production  of  the  nervous  phenomena.  The  lesions  of  the 
organs  concerned  in  the  transformation  or  elimination  of  the  poisons, 
notably  I'll"  liver,  kidneys,  and  lungs,  play  an  additional  rdle,  as  do 
likewise  the  various  conditions  favorable  to  the  production  of  toxins, 
the  virulence  of  Hie  microbe,  rapid  dii  b  isimilation,  and  hyperpyrexia. 
Thus,  deliriuni  niiiy  :i.p|)e:ir  in  consequence  of  lesions  of  an  apparatus 
which  until  Mien  was  intact,  for  instance,  the  kidneys  or  lunj 

These  ordinary  reactions  have  a  common  basis.  Although  they  are 
identical  in  all  diseases,  they  al  times  presenl  peculiar  characters  due 
to  the  action  of  specific  products  secreted  by  microbes  and,  more 
particularly,  to  the  inherited  or  acquired  predisposition  of  the  sub- 
ject. 

It  may  be  stated  that,  in  a  great  number  of  cases,  morbid 
manifestations  represent  functional  reactions  and  simply  expr 
disturbance  of  the  nervous  system;  it  is  conceivable,  however,  that 
the  prolongation  or  repetition  of  the  derangement  may  result,  more 
or  less  rapidly,  in  anatomical  alterations.  It  is  very  difficult  to  say 
at  what  moment  the  functional  disturbance  gives  way  to  anatomical 
lesion.  It  may  even  be  doubted  whether  the  distinction  is  well 
founded.  In  cells  which  no  longer  discharge  their  functions  in  a 
normal  manner  the  protoplasm  must  certainly  undergo  alteration-, 
although  these  changes  are  not  appreciable  until  they  become  suf- 
ficiently well  pronounced. 

When  the  nervous  affection  becomes  apparent  during  the  course 
or  at  the  end  of  the  disease,  the  etiology  is  evident,  but  when  months 
or  years  elapse  between  recovery  from  the  first  disease  and  the 
appearance  of  nervous  phenomena,  the  problem  then  becomes  highly 
complex;  hence  the  origin  and  connection  of  the  nervous  symptoms 
have  long  been  a  matter  of  delicate  discussion. 

At  the  present  day  there  can  no  longer  be  any  doubt,  since  experi- 
mental pathology  has  succeeded  in  producing  in  animals  a  series  of 
nervous  affections,  and  notably  myelitis,  by  means  of  inoculations 
with  more  or  less  virulent  germs.  Accurate  clinical  observation  has 
finally  removed  the  last  shadow  of  doubt.  It  may  now  be  affirmed 
that  all  nervous  affections,  save  family  and  hereditary  diseases,  are 
caused   by   some  infection    or   intoxication.     The  best  differentiated 


404  IXFECTIO  US  DISEASES. 

clinical  types  may  follow  the  most  varied  infections.  In  the  presence 
of  this  new  pathogenic  view  we  must  not,  however,  lose  sight  of  the 
role  of  predisposition,  which  alone  enables  us  to  explain  the  localiza- 
tions of  the  process. 

Infection  may  also  provoke  the  appearance,  aggravation,  or  return 
of  latent,  slight,  or  past  manifestations.  It  is  known  that  infection 
often  acts  as  a  provocative  agent  for  certain  neuropathies,  particu- 
larly hysteria. 

After  the  reactionary  phenomena  we  may  mention  the  secondary 
localizations  of  infectious  processes.  It  suffices  to  cite,  for  instance, 
tubercles,  abscesses,  and  gummata  of  the  nerve  centres  and  their 
envelopes.  These  lesions  acquire  no  particular  character  from  their 
localization.  Pathogenic  agents  colonize  in  the  nerve  centres  as 
they  do  in  other  parts  of  the  organism,  and  there  give  rise  to  reactions. 

Instead  of  being  secondary,  an  infectious  localization  is  at  times 
primary.  The  pathogenic  agent  attacks  the  nervous  system  from 
the  beginning.  It  may  be  propagated  into  the  nerve  centres  or, 
having  vegetated  at  some  other  point  of  the  economy,  secrete  soluble 
substances  which  reach  and  become  fixed  in  the  nerve  centres.  As 
illustrations  we  may  cite  hydrophobia  and  tetanus. 

These  distinctions  are  of  great  theoretical  importance.  In  prac- 
tice, however,  it  is  often  difficult  to  determine  the  mechanism  set  in 
motion.  It  is  therefore  necessary,  for  the  description  of  facts,  to 
consider  them  from  the  clinical  standpoint  and  simply  pass  in  review 
the  manifestations  which  may  occur  in  the  various  parts  of  the 
nervous  system,  namely,  the  brain,  the  medulla  oblongata,  the  spinal 
cord,  and  the  peripheral  nerves. 

Cerebral  Manifestations.  The  influence  of  infectious  diseases  upon 
the  brain  may  be  expressed  by  two  orders  of  phenomena:  (1)  diffuse 
manifestations,  such  as  headache,  incapacity  for  work,  cerebral 
obnubilation,  delirium,  and  convulsions;  (2)  symptoms  indicating 
focal  lesions,  such  as  aphasia  and  hemiplegia. 

The  necropsy  sometimes  reveals  a  focus  of  softening  due  to  an 
embolus  or  thrombus;  at  other  times,  acute  encephalitis,  a  cerebral 
abscess,  a  meningitis,  or  a  thrombosis  in  the  sinuses.  Such  marked 
lesions  are  seldom  met  with.  In  the  great  majority  of  cases  there 
is  found  simply  a  congestion  and,  at  times,  slight  hemorrhage.  In 
some  instances  a  slight  serous  effusion  is  detected  in  the  meshes  of 
the  pia  mater  and  in  the  ventricles.  Lesions  of  this  kind  are  encoun- 
tered, especially  in  typhoid  fever.     In  this  disease  more  profound 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM,       \>,:, 

alterations  are  sometimes   me1   with,    uch   a     arteritis,  menii 
hemorrhages,  and  cerebral  absce   i 

A  last  group  comprises  tho  e  cases  in  which  the  necropsy  if  nega- 
tive: the  brain  appears  healthy.  In  uch  case  the  cerebral  symp- 
toms have  been  attributed  to  circulatory  disorders,  pyrexia,  and 
mierobic  localizations.  Ii  is  now  known  thai  the  question  is  one  of 
intoxication  of  ili<i  organism  by  tnicrobic  products  and  by  waste  ol 
cellular  nutrition.  Ii  is,  therefore,  perfectly  intelligible  thai  results 
should  greatly  vary  according  to  the  nature,  intensity,  or  duration 
of  (lie  infectious  process. 

Cephalalgia.  Cephalalgia  is  observed  in  all  febrile  processes;  it 
assumes  a  certain  importance  in  several  diseases.  It  is  particularly 
interesting  to  study  headache  in  typhoid  fever.  It  often  constitutes 
the  first  symptom  of  ihe  disease.  A  pcrsistonl  headache  accom- 
panied by  some  gastric  disturbances,  ocfurrin.tr  in  a  young  person 
who  has  been  a  short  time  in  a  greal  city,  should  immediately  sugg 
typhoid  fever.  During  the  stationary  stage  headache  persists;  it  is 
generally  very  severe,  and  the  patient  refers  his  insomnia  to  it.  In 
cases  of  moderate  intensity,  headache  lasts  to  the  end  of  the  evolu- 
tion; in  graver  cases  it  disappears,  overcome  by  the  stupor  which 
invades  the  patient.  When  the  question  is  one  of  those  slight  forms 
designated  as  "walking  typhoid  cases"  headache  is  often  the  only 
symptom,  and  thus  acquires  great  diagnostic  value. 

Cephalalgia  is  less  marked  in  the  eruptive  fevers.  Measli  -  is 
attended  by  hardly  any  headache,  and  the  slight  pain  seems  to  be 
referable  to  the  coryza.  It  is  more  intense  in  variola  and  scarlet 
fever,  but  generally  ceases  with  the  appearance  of  the  eruption.  The 
return  of  headache  during  convalescence  is  often  the  first  sign  of  a 
renal  complication. 

We  must  also  note  the  importance  of  headache  in  various  forms 
of  malaria.  It  is  often  one  of  the  first  morbid  phenomena.  Its 
appearance  in  a  man  who  has  just  passed  through  a  swampy  country 
should  immediately  suggest  malarial  infection.  It  is  one  of  the  best 
premonitory  symptoms.  It  is  also  one  of  the  first  symptoms  of  the 
intermittent  paroxysm;  cephalalgia  precedes  the  chills,  persists 
during  the  cold  stage,  and  diminishes  during  the  stage  of  heat.  When 
it  occurs  in  the  intervals  of  paroxysms  the  development  of  a  per- 
nicious character  is  to  be  feared.  Finally,  after  cure  of  the  febrile 
paroxysms,  headache  may  recur  in  a  regular  manner:  it  then  repre- 
sents a  form  of  masked  malaria  which  is  not  rare  in  Europe. 


406  INFECTIO  US  DISEASES. 

At  times  headache  indicates  a  cerebral  complication ;  it  may  mean 
involvement  of  the  meninges,  especially  in  those  cases  in  which  a 
suppurative  lesion  of  the  nose  or  ear  exists.  It  is  well  to  note  that, 
contrary  to  classical  opinion,  meningites,  even  of  suppurative  type, 
are  often  latent,  ami  give  rise  to  no  reaction  and,  notably,  to  no  pain. 

Besides  headache,  the  patient  not  infrequently  complains  of  ver- 
tigo. This  symptom  is  especially  marked  in  influenza  and  typhoid 
fever.  In  the  latter  disease  it  is  manifested  as  soon  as  the  patient 
changes  position  or  sits  up  in  bed.  At  the  beginning  of  the  infection, 
when  the  diagnosis  is  yet  doubtful,  this  phenomenon  possesses  certain 
semiological  value. 

Delirium.  The  frequency  and  clinical  appearance  of  delirium 
depend  upon  two  factors:  the  state  of  the  subject  and  the  nature  of 
infection. 

The  age  of  the  patient  plays  a  very  important  role.  Children  are 
often  subject  to  delirium,  except,  of  course,  in  the  first  years  of  life, 
when  the  cerebral  centres  are  not  sufficiently  developed  for  reacting. 
The  newly-born  is  a  medullary  being,  and  the  infectious  manifesta- 
tions are  the  result  of  the  action  upon  the  spinal  cord.  Delirium  is 
of  very  frequent  occurrence  in  adults ;  it  is  less  frequent  in  the  aged ; 
the  latter  are  more  apt  to  be  attacked  by  torpor  and  adynamia. 
While  more  common  in  debilitated  or  overworked  persons,  and  in 
women  more  than  in  men,  delirium  is  particularly  influenced  by 
hereditary  or  personal  antecedents  of  the  patient.  Certain  individ- 
uals predisposed  by  heredity  become  delirious  on  the  occasion  of  any 
febrile  process ;  it  is  a  mild  form,  and  ceases  as  soon  as  the  attention 
of  the  sufferer  is  fixed.  Acquired  predisposition  is  generally  due  to 
previous  affections,  mainly  to  intoxications.  Alcoholism  plays  the 
principal  role  and  gives  rise  to  well-known  special  disturbances 
described  under  the  name  delirium  tremens.  This  is  an  event  occur- 
ring in  the  course  of  a  chronic  intoxication  and  as  a  result  of  an 
abrupt  shock.  It,  therefore,  generally  appears  in  diseases  character- 
ized by  a  sudden  onset,  such  as  variola,  scarlatina,  erysipelas,  rheu- 
matism and,  above  all,  in  pneumonia.  It  is  exceptional  in  those 
infections  which,  like  typhoid  fever,  set  in  slowly,  and  progressively. 

From  a  general  standpoint,  delirium  is  manifested  in  three  different 
degrees:  1.  Mild  delirium,  generally  bearing  upon  the  habitual  occu- 
pations of  the  patient  and  ceases  when  his  attention  is  called  to  it. 
2.  Delirium  characterized  by  the  muttering  of  incoherent  speech,  and 
often  accompanied  by  sensory  hyperesthesia,  which  explains  the  hal- 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      407 

Lucinations  and  illusions  of  sighl  and  of  hearing.  •'».  Furiou  delirium 
is  one  of  action:  the  patienl  howls,  sings,  recognizee  nobody,  an 
no  questions.  Sensibility  is  diminished.  The  sufferer  is  detached 
from  the  externa]  objective  world,  and  i  seized  with  terrifying  hal- 
lucinations. Willi  haggard  ;md  conge  ted  eyes  and  trembling  Limbs 
he  leaves  Ins  bed  and  inns  about  the  room, fighting  those  who 
to  arrest  or  calm  him. 

The  delirious  manifestations  of  the  stationary  period  generally 
disappear  at  the  end  of  i tie  disease.  In  certain  instances,  howi 
some  trouble  of  the  intellect  or  memory  may  persist.  In  other* 
more  serious  phenomena  appear.  Such,  for  example,  is  the  condition 
described  by  alienists  under  the  name  mental  confusion.  It  occurs 
in  the  most  varied  diseases:  in  typhoid  lexer,  variola,  cholera,  influ- 
enza, pneumonia,  and  erysipelas.  The  ideas  of  the  victim  are  bo 
confused  that  he  utters  only  fragments  of  phrases;  his  language 
becomes  unintelligible.  His  perceptions  are  not  clear.  His  face  is 
weak  and  stupid.  In  spite  of  their  apparent  gravity,  however, 
these  troubles  are  in  most  cases  transitory,  and  gradually  disap- 
pear. 

Post-infectious  Delirium.  Mania  may  occur  in  consequence  of  the 
most  varied  infections:  typhoid  fever, rheumatism, erysipelas, erup- 
tive fevers,  cholera,  etc.  On  consulting  a  treatise  on  mental  path- 
ology it  will  be  seen  that  the  most  varied  clinical  types  of  mental 
diseases  may  occur  as  a  result  of  an  infection.  The  same  dia 
are  mentioned  in  the  etiology  of  manias,  mental  degenerations, 
various  forms  of  insanity,  and  even  of  general  paralysis.  Their  rela- 
tive frequency  is  not  exactly  the  same.  Thus,  mental  degenerations, 
accompanied  or  unattended  by  bodily  degenerations,  are  the  inflic- 
tions of  hereditary  syphilis:  they  are  also  observed  after  typhoid 
fever,  but  are  exceptional  after  other  infections,  such  as  the  eruptive 
fevers,  diphtheria,  mumps,  and  whooping-cough.  In  the  etiology  of 
general  paralysis  (aside  from  the  influence  of  syphilis,  which  Mill  be 
referred  to  later)  are  cited  typhoid  fever,  influenza,  pneumonia,  diph- 
theria, variola,  and  especially  erysipelas. 

Tubercular  Insanity.  Although  insanity  is  at  times  consecutive 
to  a  transitory  disease,  it  may  also  occur  in  the  course  of  a  chronic 
infection,  such  as  syphilis  or  tuberculosis.  The  relationship  between 
insanity  and  phthisis  has  been  repeatedly  studied.  Alienists  have 
long  noted  the  frequent  coincidence  of  the  two  processes,  the  fre- 
quency of  tuberculosis  among  the  ancestors  of  the  insane,  and  at 


408  INFECTIOUS  DISEASES. 

times  the  alternation  of  thoracic  symptoms  and  of  cerebral  disorders 
in  the  same  individual. 

The  mental  state  of  the  tubercular  is  often  very  peculiar.  Their 
optimism  and  indifference  is  a  matter  of  common  observation.  Some 
of  them  recognize  their  state  and  accept  it  with  resignation.  How 
different  is  this  from  the  alarm  into  which  most  people  are  thrown 
on  the  slightest  morbid  manifestation.  Certain  tubercular  subjects, 
however,  are  of  a  different  temper;  they  always  complain,  and 
nothing  satisfies  them.  Others  become  suspicious,  and  may  believe 
themselves  to  be  objects  of  persecution. 

Finally,  at  the  terminal  period,  intellectual  derangements  appear, 
as  a  rule.  They  occur  tardily,  however;  a  violent  delirium  with  hal- 
lucination is  a  symptom  of  approaching  death. 

In  certain  cases  a  paroxysm  of  true  insanity  may  occur  in  the  course 
of  ordinary  tuberculosis.  We  had  the  opportunity  to  observe  a  case 
of  this  kind  in  which  very  marked  disorders  evolved  in  successive 
periods,  characterized  by  alternating  manifestations  of  depression 
and  excitation. 

Role  of  Infections  in  the  Development  of  General  Paralysis. 
Among  the  maladies  of  infectious  origin,  general  paralysis  deserves 
first  mention.  It  follows  typhoid  fever,  pneumonia,  diphtheria, 
variola,  and,  as  has  been  shown  by  Bayle  and  Baillarger,  especially 
erysipelas.  The  influence  of  syphilis  seems  also  to  be  undeniable. 
Sj^hilitic  general  pseudoparalysis,  however,  must  be  distinguished 
from  true  general  paralysis.  The  former  is  connected  with  diffuse 
syphilitic  lesions  and  is  remarkable  for  the  existence  of  certain 
peculiar  symptoms — i.  e.,  ptosis,  strabismus,  local  paralyses,  and 
cephalalgia.  Delirium  is  slight  and  often  assumes  the  circular  form. 
Finally,  its  course  is  different;  it  is  often  regressive,  and  a  cure  may 
be  effected  by  specific  treatment.  Aside  from  this  somewhat  peculiar 
clinical  type  it  must  be  recognized  that  syphilis  is  too  frequently 
found  in  the  antecedents  of  general  paralytics  to  be  simply  an  acci- 
dental coincidence.  Syphilis  does  not,  however,  produce  general 
paralysis ;  it  fulfils  here  the  same  role  as  in  the  development  of  loco- 
motor ataxia:  it  is  an  auxiliary  cause  acting  upon  predisposed 
individuals. 

Obnubilation  and  Coma.  Infections  often  give  rise  to  an  obnu- 
bilation sufficiently  pronounced  to  border  on  coma.  It  is  a  nervous 
depression  supervening  at  once  or  following  phenomena  of  excitation, 
notably  delirium. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       KM) 

Cerebral  obnubilation  is  very  marked  in  typhoid  fever,  typhus, 
and  pneumonia  in  the  aged.  If  al  o  characterise  one  of  the  forme 
of  pernicious  malarial  fever.  In  the  cour  e  of  the  eruptive  fevers  il 
presents  a  certain  diagnostic  value  according  to  the  date  of  ito  appear- 
ance. At  the  beginning  of  scarlatina  and  mea  le  a  semicomatose 
state  is  not  a  symptom  of  extreme  gravity,  al  leasl  in  children.  It. 
however,  it  does  not  subside  a1  the  time  of  eruption  the  prognosis 
becomes  grave. 

The  appearance  of  coma  during  convalescence  indicates  a  compli- 
cation and  particularly  a  bronchopneumonia  in  a  case  of  measles, 
and  a  nephritis  in  a  ease  of  scarlatina. 

These  comatose  manifestations  are  a1  all  events  rare.  With  their 
study  we  have  completed  the  consideration  of  diffuse  cerebral  mani- 
festations. We  shall  now  review  certain  phenomena  which  seem  to 
indicate  a  more  precise  localization. 

Aphasia.  Aphasia  may  occur  unassociated  with  hemiplegia.  It 
appears  during  convalescence  from  the  eruptive  fever-,  erysipelas, 
and  particularly  typhoid  fever.  It  is  mosl  frequently  observed  in 
children.  At  any  rate,  the  trouble  is  incomplete  and  transitory,  and 
recovery  is  effected  in  two  or  three  weeks.  Leyden  attributes  it  to 
a  focus  of  slight  encephalitis.  Certain  cases  mighl  perhaps  be  ex- 
plained by  neurotic  disorders,  as  we  are  led  to  believe  by  observation 
of  a  case  of  measles  in  a  girl,  three  years  of  age,  who,  two  days  after 
the  fall  of  the  fever,  had  frequent  fits  of  hysteria,  and  at  the  same 
time  lost  the  use  of  language,  save  two  words,  "Boni,  madame," 
which  was  her  invariable  reply  to  all  questions.  This  aphasia  lasted 
fifteen  days  and  then  gradually  disappeared. 

We  must  not  overlook  aphasia  occurring  in  malaria.  In  some  ci  -  - 
the  disturbance  of  speech  appears  after  a  regular  paroxysm:  it  is 
transitory  and  not  serious.  At  times  it  manifests  itself  in  a  per- 
nicious paroxysm  and  is  of  grave  prognostic  significance. 

Hemiplegia.  Hemiplegia  may  be  produced  by  various  mechan- 
isms. It  may  be  due  to  emboli  derived  from  a  clot  of  phlebitis 
vegetations  of  an  ulcerative  endocarditis.  In  the  latter  instance  the 
symptom  acquires  a  certain  diagnostic  value.  "When  the  diagnosis 
is  doubtful  as  to  the  nature  of  infection  observed — when,  for  example, 
typhoid  fever  is  thought  of — the  sudden  appearance  of  hemiplegia 
will  lead  to  a  more  careful  examination  of  the  heart,  and  thus  enable 
the  physician  to  recognize1  the  nature  of  the  events. 

Hemiplegia   dependent  upon  a  focus  of  cerebral   arteritis  is  an 


410  INFECTIOUS  DISEASES. 

incident  of  rare  occurrence.  "We  have  observed  a  case  of  this  kind, 
that  of  a  man,  thirty-three  years  of  age,  who,  consecutively  to  a 
gastroenteritis,  developed  a  right  hemiplegia  involving  the  limbs 
and  the. face,  but  sparing  the  orbicularis  palpebra?.  The  necropsy 
revealed  an  acute  arteritis  in  the  arch  of  the  aorta  and  red  softening 
occupying  the  middle  of  the  ascending  convolutions  on  each  side  of 
Rolando's  fissure,  affecting  quite  deeply  the  cortical  part. 

Hemiplegia  is  not  extremely  rare  in  pneumonia,  at  least  in  the 
aged.  It  sets  in  after  an  apoplectic  attack  and  is  often  attended  by 
conjugate  deviation  of  the  head  and  the  eyes.  Death  occurs  within 
a  few  days  in  coma.  At  the  necropsy  cerebral  softening  is  discov- 
ered. According  to  Straus,  this  lesion  is  constant,  but  so  small  as  to 
easily  escape  notice. 

There  are  also  transitory  hemiplegias  observed,  particularly  during 
convalescence  from  infections,  but  they  are  extremely  rare. 

Convulsions.  As  infantile  poliencephalitis  is  less  frequent  than 
poliomyelitis,  owing  to  the  fact  that  in  children  the  brain  is  less 
active  than  the  spinal  cord,  the  same  is  true  of  delirium  which,  in 
children,  is  replaced  by  convulsions,  especially  in  those  predis- 
posed by  heredity  or  innateness.  When  they  occur  at  the  beginning 
of  infections  they  are  not  of  grave  diagnostic  significance.  They 
often  accompany  the  invasion  of  an  eruptive  fever,  angina,  and 
notably  pneumonia.  In  the  last-named  disease  convulsions  are 
observed  chiefly  in  children  under  two  years  of  age,  thus  justifying 
the  assumption  of  an  eclamptic  form. 

Tardy  convulsions,  unlike  early  ones,  frequently  announce  the 
development  of  some  complication.  In  measles  they  must  suggest 
bronchopneumonia;  during  convalescence  from  scarlatina  they  gen- 
erally constitute  the  first  symptom  of  nephritis.  In  other  instances 
they  express  some  lesion  of  the  nervous  centres,  and  are,  for  example, 
related  to  the  development  of  meningitis.  If  convulsions  occur  in 
the  course  of  a  whooping-cough,  without  aggravation  in  the  general 
state  of  the  patient  and  without  production  of  fever,  they  are  to  be 
attributed  to  an  exaggeration  of  the  nervous  reactions  induced  by 
the  disease :  the  local  convulsion  is  generalized.  On  the  other  hand, 
if  at  the  same  time  there  is  persistent  dyspnea  and  a  rise  in  tem- 
perature, the  patient  must  be  examined  with  greater  care,  and  almost 
always  bronchopneumonia  will  be  discovered. 

Finally,  as  the  majority  of  adults  succumb  in  delirium,  so  most 
children  under  two  years  of  age  die  during  terminal  convulsions. 


influence  OF  INFECTIONS  UPON  THE  ORGANISM.       ill 

They  behave  at  I  lie  cud  of  infection  ■■>    they  do  al  Hi'-  beginning, 
presenting  nervous  reactions  which  are  referable  to  the  jame  i 
as  in  adults,  but  :ue  localized   in   differenl  parts   of   the  nervous 
system. 

Convulsions  are  quite  uncommon  in  adults.  Scarlatinal  nephritis, 
which  produces  convulsive  uremia  in  children,  gives  rise  to  dyspneic, 
delirious,  or  comatose  uremia  in  adults.  Puerperal  eclampsia  i-  an 
exception  to  (his  rule;  si  ill,  in  not  :i  U-w  cases  puerperal  uremia  is 
expi'essed  l>y  oilier  n i : 1 1 1 i festations,  notably  by  ;i  violent  delirium 
which,  in  the  absence  of  an  examination  of  the  mini',  would  very 
likely  be  mistaken  For  a  phenomenon  of  acute  insanity. 

Bulbar  Manifestations  of  Infections. 

The  majority  of  infections  affect  the  bulbar  centres.  Fevers  seem 
to  be  dependent  upon  dynamic  modifications  produced  in  the 
medulla  oblongata.  Certain  phenomena  accompanying  fever, 
notably  chills,  are  also  referable  to  a  bulbar  influence. 

The  medulla  oblongata  also  contains  centres  governing  the  func- 
tions of  the  principal  organs.  Various  cardiac  disturbances  are  of 
bulbar  origin.  Acceleration  of  pulse  in  fever  is  no1  simply  due  to 
the  rise  in  temperature,  for,  if  such  were  the  case,  it  would  follow 
nearly  the  same  course  in  all  diseases.  The  fact  is,  however,  that 
certain  diseases  affect  far  more  than  others  the  number  of  pulsations 
and  are  precisely  those  maladies  which  most  easily  excite  nervous 
reactions.  In  this  respect  scarlatina  is  the  leading  affection.  In 
this  disease,  for  the  same  degree  of  temperature,  the  pulse  is  far  more 
rapid  than  in  other  infections.  This  is  even  a  valuable  diagnostic 
symptom,  since  it  enables  the  physician  to  state,  prior  to  the  eruption, 
that  the  sore  throat  is  probably  of  scarlatinal  nature.  On  the  other 
hand,  slowness  of  pulse  may  express  the  influence  of  an  infection 
upon  the  bulb,  and  such  slowness,  coinciding  with  the  thermal  ele- 
vation, becomes  a  striking  feature.  In  a  man.  twenty-one  years  of 
age,  suffering  from  a  serious  scarlatina  complicated  with  albuminuria. 
the  number  of  pulsations  fell  to  52,  although  the  temperature  was 
102.2°  F.  (39°  C).  This  state  persisted  for  three  .lays.  It  was  prob- 
ably due  to  a  bulbar  disorder,  since,  under  the  influence  of  a  small 
dose  of  atropine,  which  diminished  the  action  of  the  pneumogastric 
nerves  without  suppressing  it.  the  pulse-rate  rose  to  64. 

We  likewise  attribute  to  disturbances  of  cardiac  and  respiratory 
centres  the  arrhythmias,  the  irregularities  of  the  heart's  action,  which 


412  IXFECTIO  US  DISEASES. 

occur  without  the  slightest  demonstrable  lesion  in  the  myocardium. 
A  similar  explanation  must  be  admitted  with  reference  to  certain 
paroxysms  of  dyspnea,  acceleration  or  retardation  in  respiratory 
movements,  which  are  accounted  for  neither  by  fever  nor  the  state 
of  the  heart,  kidneys,  or  lungs. 

The  Spinal  Cord  in  Infections. 

The  participation  of  the  spinal  cord  in  infectious  processes  is 
demonstrated  beyond  dispute  by  the  study  of  two  diseases:  one 
caused  by  multiplication  of  the  pathogenic  agent,  the  other  by  the 
action  of  microbic  toxin — we  refer  to  hydrophobia  and  tetanus.  In 
hydrophobia  the  pathogenic  agent  acts  by  means  of  the  products 
which  it  secretes.  When,  after  having  been  freed  from  all  figurate 
elements,  an  emulsion  of  the  spinal  cord  of  hydrophobic  animals  is 
injected  into  dogs,  paralytic  phenomena  are  produced.  It  is  an 
intoxication,  not  an  infection,  since  the  cord  of  these  inoculated  dogs 
is  not  virulent. 

This  toxin  is  produced  in  the  various  parts  of  the  nerve  centres, 
and  these  are  invaded  successively,  not  simultaneously.  The  patho- 
genic agent  slowly  propagates  and  colonizes.  The  experiments  of 
Di  Yestea  and  Zagari  show  that  the  introduction  of  the  virus  into 
the  sciatic  nerve  causes  a  more  marked  paralysis  on  the  side  into 
which  the  inoculation  is  made,  and  that  the  tail  of  the  horse  becomes 
virulent  before  the  medulla  oblongata.  Clinical  observation  is  in 
harmony  with  these  experimental  facts ;  it  shows  that  convulsive  or 
paralytic  phenomena  are  often  more  pronounced  on  the  bitten  side. 
According  to  the  remark  of  the  authors  above  mentioned,  a  bite  in 
the  lower  extremities  commonly  gives  rise  to  paraplegia,  while  the 
rabid  forms  usually  occur  when  the  initial  lesion  is  inflicted  on  the 
head  or  upper  extremities. 

Of  the  two  clinical  forms  of  hydrophobia,  one,  the  rabid  form,  is 
in  fact  characterized  by  the  predominance  of  cerebral  manifestations ; 
the  other,  the  dumb  or  paralytic  type,  by  the  prevalence  of  spinal 
phenomena.  These  two  forms  may  be  encountered  in  all  animals,  but 
their  relative  frequency  varies  from  one  species  to  another.  The 
rabid  form  is  more  frequent  in  the  dog,  while  in  the  rabbit  the  disease 
almost  constantly  assumes  the  paralytic  form. 

Anatomical  pathology  shows,  on  the  other  hand,  that  the  lumbar 
spine  is  affected  if  the  person  is  bitten  in  the  lower  extremities;  if 
the  wound  is  received  in  the  upper  extremities  the  cervical  spine  is 


INFLUENCE  OF  INFECTIONS  i  r<>\  THE  ORGANISM.       |]:; 

found  to  be  the  seal  of  alteration!  .  the  e  alteration*  consisting  nol 
in  mere  congestion,  bu1  in  tnall  foci  of  Boftening.  Microscopic  or 
even  larger  hemorrhages  resulting  from  the  rupture  of  congested  cap- 
illaries as  well  as  thrombosis  are  le  ion  of  frequent  occurrence.  The 
in 'I've  cells  are  altered  jal  some  points  they  are  destroyed  and  replaced 
by  masses  of  embryonal  elements  or  neuroglia  tissue. 

In  view  of  the  results  furnished  by  experimentation  and  clinical 
observation  we  may  state,  in  conclusion,  thai  the  agent  of  hydro- 
phobia is  essentially  a  parasite  of  I  he  QervoiM  system,  the  peripheral 
prolongations  of  which  it  follows  in  order  to  reach  and  localize  itself 
in  the  nerve  centres  and  there  produce  its  toxin.  Accordh 
the  ancient  expression  of  Romberg,  hydrophobia  may  therefore  be 
said  to  he  a  toxoneurosis;  we  must  only  add:  an  infectious  and 
specific  toxoneui'osis. 

Tetanus.  The  second  infectious  t < >xoneurosis  known  i-  tetanus. 
It  essentially  differs  from  the  preceding  infection  in  that  the  patho- 
genic agent  remains  localized  at  the  point  of  introduction  and  secretes 
toxins  which  follow  the  nerves  in  order  to  reach  the  spinal  cord,  the 
bulb,  and  the  brain.  Its  mode  of  action  ha-  been  and  is  -till  a 
matter  of  discussion.  Courmont  and  Doyon  believe  its  action  to  he 
that  of  a  ferment  which  gives  rise  to  a  new  poison  of  a  convulsifying 
character.  Others,  following  Ehrlich,  admit  a  combination  of  the 
toxin  with  the  protoplasm  of  the  nerve  cells,  an  intracellular  trans- 
formation thus  being  effected. 

It  remains  to  determine  what  part  of  the  nervous  system  is  the 
starting  point  of  the  disorders.  Pathological  anatomy  having 
afforded  no  conclusive  results,  physiological  analysis  must  be  resorted 
to.  At  present  there  is  general  agreement  for  localizing  the  disorder 
in  the  cord  and  the  medulla  oblongata :  and,  following  Courmont  and 
Doyon,1  it  is  admitted  that  the  process  is  one  of  exaggerated  sensi- 
tiveness of  the  reflex  axis,  the  poison  acting  probably  upon  the 
sensory  neuron.  This  conclusion  is  in  perfect  harmony  with  the 
results  of  experiments  made  by  the  author  as  regards  the  sensitive- 
ness of  tetanic  animals  to  the  action  of  strychnine.2 

Guinea-pigs,  from  two  to  seven  days  after  inoculation  with  tetanic 
toxin,  received  beneath  the  skin  small  doses  (from  0.5  to  1  mg 
strychnine   sulphate.     They   presented   convulsions    and.    in   most 

1  Courmont  and  Doyon.     Le  tetano*.     Actualites  medicates.  1899,  vol.  i. 
:  Roger.     Action  de  la  strychnine  et  du  chloral  sur  le<  animaux  tetanique*.     Soc.  de 
biologic.  May  20.  1899. 


414  INFECTIOUS  DISEASES. 

cases,  soon  succumbed.  Control  guinea-pigs  withstood  the  same 
amounts  of  the  alkaloid  without  presenting  the  slightest  disturbance. 

Infectious  Myelites  in  Man.  Numerous  facts  of  comparative  and 
experimental  pathology  demonstrate  the  frequency  of  paralyses  of 
spinal  origin  consecutive  to  infections.  In  clinical  experience  it  is 
often  difficult  to  determine  a  localization.  The  symptoms  may 
depend  upon  very  different  processes.  Three  diseases  or  rather  three 
clinical  types  may  be  referred  to  infection.  These  are  the  acute 
ascending  paralysis,  infantile  paralysis,  and  acute  spinal  paralysis 
of  the  adult.  Their  history  will  complete  the  teachings  already  fur- 
nished by  the  study  of  hydrophobia  and  will  enable  us  to  better 
appreciate  the  complex  facts  to  be  later  described. 

Acute  Ascending"  Paralysis.  Acute  ascending  paralysis  or  Lan- 
dry's disease  may  occur  in  typhoid  fever  (Landry,  Leudet,  Pitres, 
and  Vaillard),  pneumonia  (Gubler  and  Landry,  Macario),  measles 
(Barlow,  Negue),  variola  (Gubler,  Bernhardt,  Gross,  Chalvet,  Oettin- 
ger,  and  Marinesco),  in  consequence  of  puerperal  septicemia  (Landry) 
or  urinal  septicemia  (Orcel  and  Stourine,  Prince),  and  consecutive 
to  suppurative  wounds  produced  by  a  vesicatory  (Landry,  Gubler). 
In  some  cases  the  invasion  is  announced  by  certain  disturbances 
attributed  to  influenza  or  an  attack  of  indigestion.  In  other  instances 
the  onset  is  characterized  by  general  manifestations,  malaise,  loss  of 
appetite,  chills,  and  especially  fever.  Finally,  as  in  all  microbic 
processes,  the  intervention  of  some  auxiliary  cause  is  often  noted  in 
the  beginning  of  the  disease,  such  as  indigestion,  cold,  overexertion, 
and  excesses,  which  favor  the  development  and  localization  of  the 
germs. 

Some  of  the  symptoms  of  the  stationary  period  indicate  the  infec- 
tious nature  of  the  malady.  First  of  all,  fever  which,  it  must  be 
acknowledged,  is  not  constant;  also  malaise,  anorexia,  and,  not  infre- 
quently, hypertrophy  of  the  spleen.  What  further  strengthens  the 
conviction  that  acute  ascending  paralysis  must  be  of  infectious  origin 
is  the  fact  that  there  is  an  infection  of  the  nervous  centres  which,  by 
its  symptoms  and  evolution,  strongly  resembles  Landry's  paralysis 
— reference  is  here  made  to  paralytic  hydrophobia.  The  perusal  of 
certain  observations  leads  to  the  question  whether  some  cases 
recorded  as  examples  of  Landry's  paralysis  are  not  due  to  the  virus 
of  hydrophobia.  Leaving  aside  this  doubtful  question,  it  is  noticed 
that  the  evolutive  analogy  leads  to  the  assumption  of  a  pathogenic 
analogy  and,  therefore,  to  a  search  for  an  animate  agent  in  Landry's 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       \  \  :, 

disease.  Researches  in  this  direction  have  already  been  pm 
wi ih  some  success.  Baumgarten  found  in  the  blood  and  organ*  a 
bacillus  resembling  thai  of  anthrax.  Marie  and  Afarinesco  obtained 
a  similar  resull .  ( tentanni  saw  numerou  tnicrobe  ranged  in  a  semi- 
lunar form  around  the  fibres  of  peripheral  nerves,  none  being  encoun- 
tered in  the  cord.  Ii  is  impossible,  however,  to  express  a  decided 
opinion  willi  regard  to  these  various  findings,  since  none  of  the 
going  authors  completed  his  investigations  by  cultivation  and  inocu- 
lations. 

In  a  case  of  Curschmann  the  symptoms  made  their  appearance  in 
the  course  of  a  typhoid  fever  and  were  ascribed  to  Eberth's  bacillus, 
which  was,  in  fact,  found  in  the  while  substance  of  the  spinal  cord. 
The  nature  of  the  microbe  was  determined  by  cultivation  and  inocu- 
lation. In  other  instances  common  or  at  leasl  non-specific  bacteria 
have  been  encountered.  The  staphylococcus  aureus  was  found  twice 
by  Eisenlohr,  the  streptococcus  in  the  case  of  (  tettinger  and  Marin- 
esco,  which  coccus  was  cultivated  in  the  case  of  Remlinger.  Lastly, 
in  a  case  in  which  microscopic  examination  had  failed  to  disclose  the 
presence  of  any  germs,  Thomas  obtained  a  culture  of  a  micrococcus 
liquefying  gelatin. 

Thus  in  nine  cases  which  have  been  more  or  less  carefully  studied 
from  a  bacteriological  standpoint  there  was  found  twice  a  bacillus 
resembling  that  of  anthrax,  twice  undetermined  microbes,  once 
Eberth's  bacillus,  twice  the  staphylococcus  aureus,  and  twice  the 
streptococcus.  In  two  other  cases,  one  observed  by  Eisenlohr,  the 
other  by  Albu,  the  research  for  bacteria  was  negative. 

From  these  somewhat  dissimilar  facts  no  definite  conclusion  can 
be  derived.  It  can  only  be  stated  that  the  majority  of  modern 
observations  lead  to  the  assumption  that  Landry's  disease  is  an  acute 
poliomyelitis  which  may  be  produced  by  the  most  varied  microbes. 

The  following  observation1  tends  to  support  this  view:  A  man, 
thirty-three  years  of  age.  ten  days  before  his  admission  to  our  hos- 
pital experienced  sensations  of  intense  cold  in  the  lower  extremities, 
and,  three  days  later,  numbness  in  the  legs,  but  no  pain  at  any  time. 
The  lower  extremities  became  progressively  weaker,  and  he  was  com- 
pelled to  lie  in  bed;  then  throat  symptoms  appeared,  upon  which  he 
was  sent  to  the  hospital.  He  suffered  a  violent  paroxysm  of  dyspnea 
on  taking  a  glass  of  milk.     His  intellect  was  intact.    Perspired  pro- 

1  Roger  and  Josue\     Un  cas  de  paralysde  ascendants  aigue.     La  Presse  mexiicale. 
July  27.  1898. 


416  ISFECTIO  US  DISEASES. 

fusely.  He  was  hoarse,  but  nothing  abnormal  was  found  in  the 
throat.  Every  time  he  drank,  however,  he  had  a  paroxysm  of  suffo- 
cation. Paralysis  of  the  lower  extremities  was  complete;  the  upper 
extremities  were  only  weakened.  There  was  also  slight  aiursthesia, 
which  was  more  marked  in  the  lower  than  in  the  upper  extremities. 
The  patellar  reflexes  were  abolished  as  well  as  the  tendon  reflexes  of 
the  upper  extremities.  Pulse  112;  temperature  101.6°  F.  (38.7°  C.) 
in  the  morning,  100°  F.  (37.8°  C.)  in  the  evening.  On  auscultation 
sibilant  and  sonorous  rales  were  heard.  He  died  in  the  night  during 
an  attack  of  dyspnea.  The  histological  examination  of  sections  of 
the  lumbar  enlargement  showed  lesions  in  the  cells  of  the  anterior 
horns,  remarkable  alike  for  their  degree,  amounting  to  an  atrophy  of 
the  nervous  elements,  and  for  their  diffusion:  nearly  all  the  cells  were 
altered.  On  bacteriological  examination  no  microbic  foci  were  found. 
We  therefore  resorted  to  cultivation  and  inoculation  in  order  to 
determine  the  cause  of  the  disease. 

With  a  sample  of  the  blood  which  was  taken  from  the  right  heart 
immediately  after  death  we  obtained  cultures  of  a  microbe  presenting 
all  the  characters  of  the  pneumococcus.  With  these  cultures  we 
made  inoculations  into  animals.  Rabbits  presented  paresis  or  spas- 
modic paralysis  in  the  hind  legs.  Their  blood,  cultivated  in  various 
media,  yielded  pure  cultures  of  the  pneumococcus. 

Our  observation  is  the  first  to  establish  the  existence  of  an  acute 
ascending  paralysis  produced  by  the  pneumococcus.  This  result  is 
not  to  be  wondered  at.  There  are  cases  on  record  showing  that  pneu- 
monia may  be  followed  by  an  ascending  paralysis.  Landry's  famous 
observation  is  an  illustration  thereof :  the  patient  had  had  an  attack 
of  pneumonia  from  which  he  had  not  completely  recovered.  He 
remained  in  that  condition  for  two  months,  and  then  developed 
paralysis,  which  killed  him  in  a  week.  It  may,  of  course,  be  objected 
that,  in  this  case,  the  lapse  of  a  long  period  of  time  between  the 
thoracic  and  spinal  manifestations  renders  impossible  the  unreserved 
admission  of  a  relationship  of  cause  and  effect. 

No  such  objections  can  be  raised  against  our  case,  which  demon- 
strates the  possibility  of  an  ascending  paralysis  of  pneumococcic 
origin.  It  is  true  that  in  our  case  the  nature  of  the  infection  could 
not  be  determined  without  the  assistance  of  bacteriology.  The  lungs 
did  not  present  the  lesions  which  the  pneumococcus  usually  produces 
therein.  It  is  well  known  to-day,  however,  that  the  pneumococcus 
is  capable  of  giving  rise  to  various  infections  without  pulmonary 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       117 

alterations.    Numerous  facts  have  been  related  to  show  thai  this 
mierobe  frequently  reaches  the  nervous  centre  .     I'  i    nol    trange, 
therefore,  that  it  r m .1  \-  also  produce  spinal  localization  , 
The  pneumococcus  isolated  by  us  poi  ei  ed  the  property  of  pro 

(hieing  in  ;i.nini:ils,  ;is  it    h:ul   done  in   man,   nerVOU     manife- ta1 

Three  of  our  rabbits  developed  paraplegia  under  its  influence.  M 
seems,  therefore,  thai  after  il  had  once  given  rise  to  spinal  disorders 
the  microbe  had  acquired  a  sorl  of  elective  harmfulnesf   for  the 

nervous  system.  A  si  udy  of  i  his  facl  led  ii-  i"  the  view  thai  microbes 
may  become  accustomed  to  a  residence  in  certain  parte  of  the  organ- 
ism, nnd  thus  always  manifest  ;i  tendency  to  localize  themselves  in 
the  same  tissue  in  ;i  predominant  or  exclusive  manner  (p.  I'd  . 

Infantile  Paralysis.  The  infectious  nature  of  infantile  paralysis  is 
established  upon  a  fairly  large  number  of  clinical  proof-.  The  spinal 
symptoms  have  at  limes  developed  consecutively  to  a  well-deter- 
mined infection;  at  oilier  limes  i hey  have  been  observed  simulta- 
neously in  a  number  of  children,  and  prevailed  in  an  epidemic  form 
(observations  of  Cordier,  Leegaard,  Medin,  Briegleb,  Cerversato, 
Auerback,  Zapped ).  These  epidemics  are  commonly  observed  during 
summer,  and  often  coexist  with  epidemics  of  polioencephalitis.  The 
symptoms  develop  at  once  or  in  consequence  of  some  infection,  such 
as  measles,  scarlatina,  or  erysipelas.  It  is  not  an  easy  matter  to  say 
whether  acute  myelites  should  be  related  to  cerebrospinal  meningitis 
and  considered  as  due  to  a  specific  microbe,  or  whether  they  are 
caused  by  ordinary  bacteria  the  pathogenic  role  of  which  has  been 
demonstrated  by  experimentation. 

The  same  reflections  are  applicable  to  the  acute  spinal  paralysis 
of  adults,  the  symptoms  and  course  of  which  recall  exactly  those  of 
infantile  paralysis  and  which  may  also  prevail  in  epidemic  form.  In 
the  report  given  by  Leegaard  fifty-four  individuals  were  affected. 
The  greatest  number  of  cases  are  observed,  on  the  one  hand,  under 
four  years  of  age,  and,  on  the  other,  between  fifteen  and  nineteen 
years;  a  few  patients,  however,  were  above  thirty.  Of  the  fifty-four 
persons  attacked,  twelve  recovered  completely :  thirty  retained  some 
paralysis;  ten  remained  impotent,  and  two  died. 

Myelites  in  Various  Infections.  Myelites  which  develop  in  the 
course  or  in  consequence  of  infectious  diseases  may  be  divided  into 
two  groups  according  as  they  are  diffuse  or  systematic. 

Diffuse  myelites  are  very  frequent,  but  they  may  at  times  t>    s 
slight  as  not  to  be  revealed  by  any  symptom.     Widal  and  Bezancon 

27 


418  INFECTIOUS  DISEASES. 

have  found,  for  example,  alterations  in  the  cells  of  the  anterior 
horns  in  two  variolar  patients  who,  during  life,  had  not  presented 
any  spinal  symptom.  One  is  thus  led  to  ask  whether  certain  motor 
difficulties  experienced  by  convalescents  and  attributed  to  asthenia 
do  not  depend  upon  superficial  and  curable  lesions  of  the  spinal  cord. 

In  certain  instances  myelitis  appears  at  the  beginning  of  an  infec- 
tion. Such  is  particularly  the  case  in  variola,  The  intense  back- 
ache of  which  patients  complain  indicates  the  early  participation  of 
the  spinal  cord  in  the  process.  There  may  be  nothing  more  than 
congestion.  It  is  known,  moreover,  that  backache  occurs  at  the 
onset  of  other  eruptive  fevers.  In  fact,  all  the  infectious  diseases 
might  be  cited  in  this  connection.  Typhoid  fever,  influenza,  pneu- 
monia, erysipelas,  dysentery,  and  gonorrhea  are  among  the  most 
frequent,  Diphtheria  might  be  added,  although  authorities  are 
greatly  inclined  to-day  to  refer  the  paralyses  of  this  disease  to 
peripheral  neuritis. 

The  symptomatology  is. extremely  variable.  In  some  instances 
disorders  rapidly  develop,  as  in  acute  ascending  paralysis ;  in  other 
cases  the  manifestations  are  at  first  diffuse,  but  subsequently  become 
localized  in  a  certain  part  of  the  spine.  At  times  the  victim  is 
paralyzed  in  the  lower  extremities  or  only  in  a  limited  part  of  the 
body.  In  the  presence  of  these  various  paralyses  the  question  arises 
as  to  whether  they  are  due  to  real  medullary  lesions  or  to  neuritis, 
neurosis,  or  hysteria.     The  question  often  remains  unanswered. 

There  can  be  no  doubt  in  the  case  of  a  well-determined  disease, 
such  as  tabes  dorsalis.  The  role  of  infection  in  the  genesis  of  this 
myelitis  is  incontestable.  Numerous  statistics  show  that  nearly 
all  sufferers  from  tabes  have  a  syphilitic  history.  This  fact,  how- 
ever, does  not  warrant  the  conclusion  that  locomotor  ataxia  is  a 
syphilitic  disease,  since  it  does  not  respond  to  the  specific  treatment, 
and  at  the  necropsy  no  lesion  is  found  presenting  the  characteristics 
of  syphilis.  In  nine  out  of  ten  cases  of  tabes  syphilis  is  said  to  be 
found  in  the  antecedents.  Granted.  The  tenth  case,  however,  is 
sufficient  to  prevent  tabes  from  being  held  as  a  syphilitic  disease. 
Syphilis  does  act,  but  only  as  an  auxiliary  cause.  Other  causes 
could,  however,  play  the  same  role,  and  this  is  proved  to  be  true 
by  the  fact  that  a  great  number  of  infections,  such  as  pneumonia, 
typhoid  fever,  cholera,  variola,  etc.,  are  often  found  in  the  antece- 
dents of  non-syphilitic  sufferers  from  tabes. 

"We  must  likewise  note  that  progressive  muscular  atrophy  ensues 


INFIjlJUNdH  OF  INFECTIONS  UPON  TEE  ORGANISM.      Hfl 

sometimes  after  infections  such  8    typhoid  fever,  mea  le  .  rheuma- 
tism, cholera,  and  pneumonia. 

Lastly,  Desnos  and  Babin  ki  nave  shown  syphili  among  the 
causes  of  syringomyelitis.  This  affection  hat  sometime*  followed 
typhoid  fever,  rheumatism,  pneumonia,  gonorrhea,  or  even  a  simple 
bronchitis. 

Infectious  Neurites. 

The  participation  of  the  peripheral  nerV0U£  ;  tem  in  infectious 
processes  is  evidenced  by  the  frequency  of  neuralgias,  notably  facial, 
sciatic,  and  intercostal  neuralgias.  Acute  as  well  as  chronic  infec- 
tions often  give  rise  to  these  nervous  manifestations.  They  have 
been  observed  as  a  result  of  influenza  and  pneumonia.  I  have  met 
with  several  examples  consecutive  to  scarlatina  and  erysipelas. 
Their  frequency  in  malaria  and  syphilis  is  well  known.  In  all  cases 
of  rebellious  sciatic  neuralgia  the  cause  of  which  cannol  be  deter- 
mined, Landouzy  advises  a  search  for  tubercular  manifestations. 

Herpes  zoster  sometimes  develops  in  consequence  of  an  infection, 
notably  erysipelas  and  scarlatina.  The  frequency  of  primary  herpes 
in  certain  seasons,  the  febrile  movement  accompanying  it,  and  the 
immunity  conferred  by  a  first  attack  seem  to  give  a  solid  basis  to 
the  opinion  that  this  eruption  depends  upon  an  infection  of  the 
nervous  system. 

The  motor  disorders  caused  b}-  peripheral  neuritis  must  lie  care- 
fully studied.  They  are  often  contrasted  with  similar  disturbances 
produced  by  medullary  lesions,  and  some  authorities  have  attempted 
to  establish  differential  characters  between  myelitis  and  neuritis. 
It  is,  perhaps,  an  error  to  separate  too  widely  the  two  process  - 
The  peripheral  alterations  possibly  depend  upon  some  central  lesion, 
though  the  latter  may  be  slight  and  easily  escape  notice,  or  be 
inappreciable  by  our  present  means  of  investigation. 

Infectious  polyneurites  are  often  divided  into  two  groups,  accord- 
ing as  they  occur  in  the  course  of  a  definite  disease  or  independently. 

Secondary  infectious  polyneurites  are  observed  in  connection  with 
all  acute  infections.     The}*  at  times  appear  in  the  course  of  chronic 
infections,  such  as  paludism,  tuberculosis,   syphilis,   and  lep- 
It  is  known  that  in  the  last-named  disease    the    bacilli    become 
localized  in  the  nerves  and  there  produce  small  noduL  - 

Primary  polyneurites  may  be  acute  or  chronic.  In  the  former 
case  they  constitute  a  clinical  type  described  by  Leyden;  in  the 


420  IXFECTIO  US  DISEASES. 

latter  instance  it  is  a  malady  of  hot  countries:  beriberi.  Balz  and 
Scheube  found  in  the  affected  nerves  a  diplococcus,  cultures  of 
which  gave  rise  to  peripheral  neuritis  when  inoculated  into  dogs 
and  rabbits. 

Acute  infectious  polyneurites  sometimes  occur  in  epidemic  form, 
as  Eisenlohr  has  observed  the  disease  in  Hamburg.  They  often  begin 
suddenly  by  intense  pain  in  the  extremities,  notably  in  the  lower, 
and  are  attended  by  fever,  at  times  delirium,  insomnia,  and  a  certain 
degree  of  stupor.  There  is  albumin  in  the  urine,  and  the  skin  may 
present  a  subichteric  aspect. 

Then  paralysis,  accompanied  with  shooting  pains,  supervenes. 
Later,  sensation  is  diminished,  and  may  sometimes  advance  to 
anesthesia,  especially  at  the  periphery  of  the  limbs.  The  paralysis 
is  of  the  flaccid  kind,  without  contracture,  and  attacks  the  lower 
extremities,  although  in  some  cases  it  may  assume  an  ascending  course 
and  also  involve  the  upper  extremities.  The  muscles  soon  become 
atrophied,  while  fat  accumulates  in  the  subcutaneous  cellular  tissue. 
Tendon  reflexes  are  diminished  or  abolished.  Electric  contractility 
of  the  muscles  is  generally  diminished,  the  reaction  of  degeneration 
is  often  observed.  In  cases  in  which  the  pneumogastric  is  in- 
volved, death  may  ensue  by  asphyxia  at  the  end  of  a  period  varying 
from  six  clays  to  a  month.  In  other  cases  the  process  is  arrested 
and  subsides;  the  patient  recovers  completely  or  else  retains  some 
paralyses. 

Pseudotabetic  polyneurites  are  readily  distinguished  from  loco- 
motor ataxia  by  the  gait  of  the  patient,  the  legs  being  lifted  high 
instead  of  groping,  by  the  absence  of  visceral  disturbances,  and  by 
favorable  evolution  of  the  lesions. 

Pseudotabes  has  been  observed  in  consequence  of  a  great  number 
of  infectious  diseases,  and  notably  after  diphtheria  and  erysipelas. 
As,  however,  these  two  diseases  are  most  frequently  attended  by 
paralytic  manifestations  of  all  descriptions,  it  is  interesting,  to  devote 
a  special  study  to  them. 

Diphtheritic  Paralyses.  In  my  personal  statistics  I  find  in  a  total 
of  216  cases  of  diphtheria  in  adults  42  attacked  by  paralysis.  In 
39  of  these  the  palate  was  paralyzed,  in  12  the  extremities  were 
also  involved.  In  nearly  half  of  the  cases  paralysis  appeared  two 
to  fifteen  clays,  exceptionally  three  to  four  weeks,  after  the  beginning 
of  the  disease. 

Motor  disturbances  may  be  accompanied  by  disorders  of  sensation 


INFLUIMCH  of  INFECTIONS  UPON  THE  ORGANISM.       121 

and  of  the  senses.    One  patienl  I"  1  ta  te,  so  thai    agar,  salt,  and 
quinine  sulphate,  when  applied  to  the  tongue,  had  a  slightly  suj 

taste  to  hi  111. 

Trousseau  has  laid  stress,  though  with  manifest  exaggeration, 
upon  tho  wandering  character  of  diphtheritic  paralyses.  In  fact, 
one  is  at  times  astonished  a1  modifications  occurring  suddenly.  A 
patient  under  my  observation  Buffering  from  post-diphtheritic 
pseudotabes  was  almost  Incapable  of  walking.  A  fire  occurred 
in  the  ward  where  he  was  lying,  and  soon  ii  was  so  full  of  smoke 
that  (hose  who  ran  to  rescue  him  were  forced  to  fall  back.  Another 
attempt  was  about  to  be  made  when  the  patienl  was  seen  coming 
out  quietly.  Under  the  influence  of  the  emotion,  paralysis  had 
suddenly  vanished,  and  recovery  proved  to  be  permanent. 

Fatal  termination  results  from  the  entrance  of  food  into  the 
respiratory  tract.  This  aecidenl  is  particularly  frequenl  when 
the  glottal  muscles  are  paralyzed  coincidently  with  the  palate.  The 
resu.lt  is  a  bronchopneumonia  or  a  pulmonary  gangrene,  invariably 
terminating  in  death.  Death  occurs  by  asphyxia,  al  times  by 
syncope. 

It  is  to  be  noted  that  the  employment  of  the  esophageal  bougie, 
far  from  preventing  the  passage  of  food  into  the  respiratory  tract, 
seems  to  favor  this  accident;  the  fluids  introduced  into  the  stomach 
are  soon  rejected  by  regurgitation,  and  enter  the  trachea.  I  have 
seen  two  patients  succumb  in  this  manner. 

In  certain  cases  death  results  from  an  unexpected  attack  of 
syncope.  A  man,  twenty-five  years  of  age,  who  had  paralysis  of 
the  palate,  died  suddenly  twenty-four  hours  after  the  beginning  of 
the  disease.  Histological  examination  demonstrated  the  integrity 
of  the  bulbar  centres  ami  pneumogastrics.  but  revealed  a  diffuse 
myocarditis,  which  had  probably  played  the  principal  role. 

There  is  at  present  an  inclination  to  believe  that  diphtheritic  angina 
is  the  only  kind  of  sore-throat  capable  of  giving  rise  to  para;;  -  s. 
Some  of  my  observations  show  this  opinion  to  be  exaggerated.  A 
woman,  of  twenty-five  years  of  age,  who  had  recovered  from  a 
phlegmon  of  the  tonsil,  retained  a  paralysis  of  the  palate:  the  fluids 
flowed  through  the  nose,  and  the  patient  was  forced  to  incline  the 
head  backward  in  order  to  swallow.  This  paralysis  disappeared 
suddenly  four  days  later.  In  face  of  this  sudden  termination  one 
may  think  of  a  hysterical  phenomenon :  no  stigmata  of  this  neurosis 
were  found,  however. 


422  INFECTIOUS  DISEASES. 

Erysipeloid  Paralyses.  Next  to  diphtheria  erysipelas  is,  perhaps, 
the  disease  which  most  frequently  gives  rise  to  paralytic  disturb- 
ances. My  former  interne,  Dr.  Crochet,  made  an  excellent  study  of 
it  in  his  thesis  (1S95). 

Trousseau  observed  impotence  of  the  dorsolumbar  muscles  con- 
secutively to  diphtheria,  rendering  vertical  position  impossible.  I 
observed  a  young  girl  of  sixteen  years,  convalescent  from  a  severe 
erysipelas,  who  was  incapable  of  sitting  up  in  her  bed  or  raising  her 
head.  On  the  following  day  she  was  able  to  get  up  and  walk  when 
supported,  but  she  had  a  tabetic  gait.  There  was  also  a  persistent 
paratysis  in  the  nape  of  the  neck.  The  phenomena  were  gradually 
ameliorated,  and  the  patient  recovered  in  a  fortnight. 

I  have  noticed  the  appearance  of  painful  spasms  and  marked 
impotence  in  the  lower  extremities  in  two  convalescents  from  ery- 
sipelas. One  of  them,  a  woman  of  twenty-one  years,  without  any 
nervous  antecedents,  suffered  from  shooting  pains  in  the  legs  after 
an  erysipelas  of  moderate  intensity.  She  could  not  stand  on  her 
feet  for  more  than  five  minutes  at  a  time;  when  she  rose,  her  legs 
remained  in  a  position  of  semiflexion,  and  her  head  fell  upon  her 
chest.  At  the  end  of  a  month  all  these  symptoms  were  almost 
completely  cured. 

In  some  cases  peripheral  paralyses  occur.  A  manifestation  of 
frequent  occurrence  consists  in  a  combination  of  paralysis  of  the 
lower  extremities  and  cutaneous  hyperesthesia  and  exaggerated 
reflexes.  In  some  instances  the  upper  extremities  are  also  involved. 
Paralysis  of  accommodation  preventing  vision  at  close  range,  facial 
paralysis,  amblyopia,  and  diminution  in  auditory  acuteness  are 
likewise  among  the  possible  events. 

Scarlatinal  Paralyses.  Of  all  the  eruptive  fevers,  scarlatina  is 
the  most  often  productive  of  paralytic  disturbances;  still,  these  are 
rare.  In  a  total  of  2213  cases  I  found  only  four  cases  of  incomplete 
paraplegia.  In  one  of  these  instances,  a  man,  who  suffered  from 
scarlatinal  angina,  developed  paralysis  of  the  palate  on  the  second 
day.  Three  days  later  the  lower  extremities  were  slightly  involved; 
next  the  right  arm  was  attacked;  movement  was  still  possible,  but 
difficult  and  maladroit.  These  symptoms  disappeared  in  ten  days. 
In  the  antecedents  of  this  man  was  found  the  occurrence  of  a  transi- 
tory paralysis  occurring  four  years  previously  as  a  result  of  some 
work  done  in  compressed  air. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       123 

Post-infectious  Neuroses. 

The  influence  of  infection  as  an  occasional  cause  of  neuro 
present  well  known,  in  mosl  ca  es  thedi  order  are  ol  a  h)  fcerical 
character.  In  a  man  convalescenl  from  scarlatina  attackf  of  con- 
vulsions occurred,  in  another,  ane  the  ia  oi  general  en  ation  and 
of  the  senses  developed  after  erysipelas .  [n  still  other  cases,  trem- 
bling is  observed;  such  was  the  ca  e  in  a  man,  ixty  nine  yean  of 
age,1  whose  trembling  was  firsl  mistaken  as  paralysif  agitans.  The 
rhythmical  oscillations  of  the  forearms  were  repeated  l  l()  to  150  times 
a  minute.  When,  however,  he  attempted  to  carry  a  glass  of 
to  his  mouth  the  trembling  changed  its  character;  instead  of  ceasing 
during  the  movement,  as  is  (he  case  in  paralysis  agitans,  the  range 
of  the  oscillations  was  exaggerated,  so  that  the  water  was  thrown 
out  and  the  patient  struck  his  face.  The  patellar  reflexes,  on  the 
other  hand,  were  diminished.  The  uncertain  diagnosis  was  singu- 
larly facilitated  by  the  study  of  his  antecedents.  He  belonged  to 
a  family  of  nervous  people.  His  father,  of  a  violent  tamper,  had 
committed  suicide  at  the  age  of  eighty-six  years,  because  he  had 
become  incapable  of  riding  a  horse.  One  of  his  sisters  has  attacks 
of  hysteria.  During  his  long  life  he  had  been  sick  only  twice:  he 
had  two  attacks  of  pneumonia,  and  here  is  the  curious  series  of 
accidents  which  were  produced  by  these  infections: 

His  first  attack  of  pneumonia  occurred  in  1S60,  at  the  age  of 
thirty-five  years.  While  being  treated  under  Bouillaud  lie  was 
subjected  to  blood-letting  fourteen  times  in  five  days.  In  spite  of 
such  treatment,  the  patient  was  too  agitated,  and  therefore  he  was 
isolated.  This  measure  irritated  him:  he  was  furious  and,  for  the 
first  time  in  his  life,  he  had  a  nervous  paroxysm,  fought,  cried,  and 
all  ended  in  profuse  sweating:  he  then  fell  into  a  sound  sleep.  On 
awakening  the  following  day  he  noticed  that  he  could  not  move 
his  lower  extremities,  and  had  retention  of  urine.  He  recovered 
from  his  pneumonia  two  days  later,  but  his  paraplegia  persisted 
unmodified.  For  a  year  and  a  half  he  wandered  from  hospital  to 
hospital,  and  finally  was  admitted  into  the  wards  of  Behier.  who 
prescribed  douches  and  extract  of  valerian.  Recovery  was  complete 
in  forty-five  days.  The  man  resumed  his  occupation  and  again 
became  as  quiet  as  ever,  no  longer  presenting  any  nervous  spells. 

1    Roger.    Du  tremble  men  t  hysterique.     La  s?maiue  medicate.  Nov.  .5.  1S93.  p.  -522. 


424  INFECTIOUS  DISEASES. 

Thirty-three  years  later,  in  1S93,  this  man  had  another  attack  of 
pneumonia.  He  easily  recovered  from  it,  but  he  experienced  an 
increase  in  the  urinary  disorder  from  which  he  had  suffered  for  some 
time  and  which  was  due  to  hypertrophy  of  the  prostate  gland.  He 
was  convalescent  when  he  tried  to  catheterize  himself,  and,  not 
succeeding,  he  became  impatient,  and  suddenly  had  a  nervous 
paroxysm  similar  to  the  one  he  experienced  in  1860.  When  he 
became  conscious  he  found  his  extremities  trembling  intensely.  The 
lower  limbs  were  rapidly  cured,  but  the  disorder  persisted  in  the 
upper  extremities,  and  it  was  for  this  reason  that  the  patient  asked 
to  be  admitted  into  our  wards  in  1893. 

There  can  be  no  doubt  as  to  the  hysterical  character  of  the  pheno- 
mena, both  paralyses  and  trembling.  This  diagnosis  was  confirmed 
by  the  fact  that  our  patient  presented  a  slight  right  hemianesthesia 
and  a  hysterogenic  zone  on  the  testicle  of  the  same  side.  The 
absence  of  ocular  disturbances,  the  diminution  of  the  patellar  reflex, 
and,  on  the  other  hand,  the  absence  of  the  characteristic  stiffness, 
were  not  consistent  with  the  idea  of  spinal  sclerosis  and  paralysis 
agitans,  diseases  the  coexistence  of  which  with  hysteria  is  not  im- 
possible. Further  developments  fully  proved  the  correctness  of  our 
diagnosis.  We  prescribed  a  daily  dose  of  4  grains  of  extract  of 
valerian.  There  was  improvement  in  a  few  days.  One  day,  after 
catheterization,  the  patient  had  an  intense  febrile  paroxysm.  The 
fever  did  not  last,  but  exerted,  it  seems,  a  favorable  influence  upon 
the  nervous  symptoms,  which  gradually  diminished,  and  between 
June  27th,  the  day  when  the  fever  occurred,  and  July  3d  it  had 
almost  completely  disappeared.  He  could  hold  a  large  object, 
such  as  a  glass,  and  could  therefore  drink  all  right,  but  he  could 
not  control  his  movements  when  handling  a  small  article  like  a 
spoon,  and  hence  he  was  not  yet  able  to  eat  his  soup.  From  this 
moment  onward  I  noted  his  improvement  day  after  day,  by  causing 
him  to  write.  At  first  he  was  able  to  use  only  a  pencil,  and  later 
a  pen.  On  awakening  in  the  morning,  while  his  bladder  was  full, 
he  wrote  with  great  difficulty;  the  characters  were  often  indented 
and  jagged  as  in  paralysis  agitans.  A  few  minutes  after  he  had 
been  catheterized  he  was  able  to  write  in  a  correct  manner.  These 
last  manifestations  also  gradually  vanished,  and  the  man  was  com- 
pletely cured  by  the  end  of  July. 

This  observation  seemed  to  me  interesting  in  more  than  one 
respect,  and  particularly  by  reason  of  the  conditions  which  governed 


INFLUENCE  OF  INFECTIONS  UPON  THE  0  BO  AN  18 M.       \j_:, 

the  development  of  the  morbid  phenomena.  Here  i  a  man  who 
presented  no  hysterical  manifestation  whatever  until  the  age  of 
thirty-five  years,  but  his  nervoui  y  tem  had  an  hereditary  taint.  A 
pneumonia  supervened  and  broke  the  unstable  tate  of  equilibrium. 
Simple  anger  sufficed  to  give  rise  to  the  gravest  manifestations. 
Then  order  was  again  restored  in  the  oervou  •  tem,  and  the  man 
led  a  perfectly  calm  life  for  thirty-three  years,  until  al  the  age  ol 
sixty-nine  years  when  man  is  commonly  secure  from  hysteria 
hysterica]  incidents  once  more  occurred,  brought  about  by  similar 
causes.  Much  has  been  said  in  recent  yen-  regarding  the  role  of 
infection  in  the  development  of  hysteria;  there  can  be  found  do 
observation  more  demonstrative  than  the  foregoing. 

In  this  connection  I  may  rile  the  r;ise  of  a  young  girl,  aged 
enteen  years,  who,  after  a  facial  erysipelas,  was  suddenly  attacked  by 
trembling  in  the  lower  extremities  and  the  forearms.  A  few  mo nth- 
after,  as  the  result  of  an  hysterical  attack,  the  trembling  suddenly 
disappeared.  This  abrupt  termination  and  the  appearance  of  hys- 
terical attacks,  which  recurred  once  :i  month  thereafter, confirm  the 
diagnosis  of  post-infectious  hysterical  trembling  made  in  the  old 
man's  case. 

In  the  case  of  a  girl  eight  years  of  age,  five  days  after  recovery 
from  scarlatina,  choreiform  movements  with  anesthesia  in  the  ex- 
tremities of  the  left  side  made  their  appearance.  A  few  days  later 
a  well-marked  hysterical  paroxysm  occurred.  In  fifteen  days  all 
symptoms  disappeared. 

Another  patient,  also  convalescent  from  scarlatina,  developed 
spasmodic  paraplegia  in  the  lower  extremities,  with  hyperesthesia, 
exaggeration  of  the  patellar  reflexes,  and  epileptoid  trepidation. 
These  manifestations  disappeared  within  a  fortnight. 

Among  hysterical  manifestations  observed  after  infections  I  may 
mention  a  case  of  aphasia  following  measles  in  an  eight-year-old 
child,  and  two  cases  of  astasia-abasia  following  scarlatina.  One  of 
the  latter  concerned  a  woman  for  ten  years  subject  to  hysterical 
attacks.     The  manifestations  soon  disappeared. 

Epilepsy,  Tetany,  Chorea.  Like  hysteria,  epilepsy  may  appear 
in  consequence  of  acute  infections,  such  as  scarlatina,  measles, 
variola,  typhoid  fever,  and  in  the  course  of  chronic  infections — 
paludism  and  syphilis.  The  same  is  true  of  neurasthenia,  which  at 
times  develops  or  is  aggravated  after  infections.  Paralysis  agitans 
has  also  been  observed  on  the  occasion  of  a  typhoid  fever,  acute 


426  ISFECTIOUS  DISEASES. 

articular  rheumatism,  and  intermittent  fever.  Tetany  has  been 
noted  under  the  same  circumstances,  notably  after  the  eruptive 
fevers,  cholera,  and  pneumonia.  Of  all  the  neuroses  chorea  occurs 
most  frequently  under  these  conditions.  Rheumatic  infection — 
since  rheumatism  is  now  admitted  to  be  an  infection — may  be  held 
to  be  the  most  frequent  cause  of  chorea.  It  seems,  however,  that 
chorea  is  to  rheumatism  what  tabes  dorsalis  is  to  syphilis :  it  is  the 
chief  occasional  cause,  nothing  more.  There  are  many  observations 
of  choreic  children  who  have  never  had  rheumatism,  but  who  have 
just  suffered  from  some  acute  disease,  an  eruptive  fever,  notably 
measles,  typhoid  fever,  cholera,  whooping-cough,  or  influenza.1 

In  a  total  of  300  chorea  cases  Triboulet  recognized  100  patients 
who  developed  the  neurosis  in  consequence  of  some  infection.  On 
the  other  hand,  on  tabulating  various  statistics,  I  find  rheumatism 
in  the  etiology  of  chorea  in  only  22  per  cent,  of  the  cases.  It  may, 
therefore,  be  concluded  that  rheumatism  plays  a  considerable  role, 
but  is  far  less  important  than  many  authorities  assert. 

Infectious  Meningites.  The  meninges,  like  the  other  parts  of  the 
organism,  may  be  infected  primarily  or  secondarily.  The  type  of 
primary  meningitis  is  represented  by  the  epidemic  cerebrospinal 
meningitis  due  to  the  meningococcus  intracellularis  of  Weichsel- 
baum.  This  pathogenic  agent  invades  the  economy  through  the 
nasal  fossae.  Primary  meningitis  may  also  be  dependent  upon 
common  bacteria ;  it  is  usually  caused  by  the  pneumococcus,  and 
represents  the  localization  of  a  bacteremia. 

The  investigation  of  microbes  in  meningitis  acquires  to-day  con- 
siderable interest,  since  it  is  possible  to  puncture  the  spinal  meninges 
during  life  and  examine  the  spinal  fluid.  By  this  new  procedure 
it  has  been  found  that  out  of  a  total  of  100  cases  of  meningites  60 
were  due  to  the  pneumococcus  (Netter) .  This  micro-organism  may 
give  rise  to  primary  meningitis,  or  else  invade  the  meninges  in  conse- 
quence of  a  pulmonary  localization ;  meningitis  is  said  to  occur  once 
in  two  hundred  cases  of  pneumonia.  The  pneumococcus  may 
likewise  act  as  a  secondary  agent  in  the  course  of  another  infection, 
notably  erysipelas. 

Next  comes  the  streptococcus.  It  produces  the  meningitis  of 
puerperal  infections  and  of  pyemias.  It  is  also  the  microbe  most 
commonly  found  in  meningitis  consecutive  to  lesions  in  the  ear. 

1  Triboulet.  Du  role  possible  de  1 'infection  dans  la  pathologie  de  la  choree.  These 
de  Paris,  1893. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       \z7 

Bacilli,  notably  the  typhoid  bacillui  ,  Friedlaender'i  bacillus,  and 
the  bacillus  of  influenza  may  also  induce  meningeal  inflammation  . 
Rheumatic  meningites  seem  to  represenl  a  localization  of  pseudo- 

rlicuiii;iJ,isnis  /.  <■.,  of  pyemias.  M  i  al  o  to  be  remembered  thai 
the  association  of  these  various  microbes  in  the  same  focus  is  not 

an  uncommon  cvcnl . 

Among  the  discuses  treated  in  our  wards,  erysipelas  furnished 
the  strangest  results.  In  a  total  of  2411  patients  we  observed 
three  cases  in  which  the  necropsy  disclosed  a  suppurative  meningitis. 
It  was  natural  to  refer  the  lesion  of  the  meninges  to  streptococcic 
infection;  bacteriological  examination  demonstrated,  however,  thai 
the  process  was  one  of  secondary  pneumococcic  infection. 

Meningitis  has  been  altogether  exceptional  in  connection  with 
other  infectious  diseases  treated  by  us.  We  find  only  four  obser- 
vations of  this  kind,  which  are  very  few  in  view  of  the  large  number, 
7778,  not  including  erysipelas,  contained  in  our  general  statistics. 
In  two  instances  meningites  were  consecutive  to  suppurative  otitis. 

Influence  of  Infection  upon  Neuropathies.  The  fact  thai  an 
infection  may  give  rise  to  nervous  disturbances  has  repeatedly  been 
referred  to.  It  produces  hysterical,  choreic,  epileptic  or  exoph- 
thalmic manifestations  in  predisposed  subjects.  Occasionally  it 
arouses  a  past  disorder.  Thus  in  a  tabetic  subject  of  forty-five 
years  of  age,  who  had  a  syphilitic  history,  an  attack  of  erysipelas 
caused  the  return  of  fulgurating  pains,  from  which  the  patient  had 
not  suffered  in  several  years.  In  other  instances  infection  engenders 
morbid  symptoms  in  apparently  healthy  individuals,  and  thus  reveals 
the  existence  of  a  latent  disease.  Such  was  the  case  in  a  man  of 
forty-eight  years,  who  had  had  syphilis  twenty-six  years  before. 
After  an  attack  of  erysipelas  he  complained  of  very  intense  hyper- 
esthesia and  lancinating  pains  in  the  lower  limbs.  Examination 
then  revealed  exaggerated  cutaneous  reflexes,  abolition  of  tendon 
reflexes,  inequality  of  the  pupils,  suppression  of  accommodation  to 
light,  slight  ataxia  in  movements,  and  inability  to  walk  with  closed 
eyes.  The  phenomena  of  cutaneous  hyperesthesia  soon  subsided, 
but  the  other  manifestations,  which  became  apparent  at  the  time 
of  the  erysipelatous  attack,  continued  their  evolution. 

On  the  other  hand,  an  intercurrent  infection  may  cause  the  dis- 
appearance of  pre-existing  nervous  symptoms.  It  may  thus  act 
upon  hysteria,  epilepsy,  and  may.  perhaps,  even  improve  organic 
lesions.     A  woman  of  forty-four,  who  had  been  treated  in  a  hospital 


428  IXFECTIO  US  DISEASES. 

for  two  vears  for  a  paraplegia  attributed  to  myelitis,  came  under  my 
observation.  During  convalescence  from  an  erysipelas  the  reflexes 
which  had  been  abolished  reappeared,  paralysis  diminished,  and 
two  weeks  later  the  patient  walked  with  ease.  No  sensory  disorder 
or  hysterical  stigmata  existed  in  this  case.  Unfortunately,  in  the 
majority  of  cases,  amelioration  is  not  permanent.  Contrary  to 
expectation,  infections  and  inoculation  of  microbic  toxins  do  not 
cure  epilepsy. 

Action  of  Infections  upon  the  Organs  of  Sense. 

The  study  of  the  organs  of  sense  usually  goes  with  that  of  the 
nervous  system. 

The  frequency  of  oculo-nasal  catarrh  at  the  beginning  of  measles 
is  familiar.  It  figures  among  the  initial  symptoms,  and  is  of  much 
diagnostic  value.  It  may,  however,  be  absent,  or  so  slight  as  to 
readily  escape  observation.  On  the  other  hand,  other  infections, 
notably  scarlatina  and  variola,  are  sometimes  attended  by  the 
symptom  under  consideration.  The  physician  must,  therefore,  be 
awake  to  this  double  source  of  error. 

During  the  stationary  period  of  and  convalecsence  from  infectious 
diseases,  complications,  generally  of  a  suppurative  character,  are 
very  frequently  observed  in  the  various  organs  of  sense.  Purulent 
rhinitis  occurring  in  scarlatina  is  sometimes  so  profuse  as  to  suggest 
glanders.  This  complication  is  quite  grave,  as  thirteen  of  such  cases 
ended  fatally. 

The  nasal  fossa?  may  also  serve  as  entrance  to  many  other  patho- 
genic germs.  In  several  instances  in  which  streptococci  had  engen- 
dered slightly  purulent  inflammation  in  the  nose,  erysipelas  developd 
a  few  daj^s  later.  The  development  of  streptococcic  dermatitis  is 
far  oftener  preceded  by  coryza  than  by  angina. 

Ocular  suppurations  are  rare.  Catarrhal  conjunctivitis  is  fre- 
quently observed,  but  it  is  slight  and  transitory,  except  in  variola. 
In  this  infection  conjunctivitis  is  frequent  and  grave.  Inflammation 
too  often  extends  to  the  cornea,  and  opacity  may  be  produced 
within  twenty-four  hours.  This  involvement  may  occur  even  when 
stagnation  of  the  septic  fluids  is  prevented  by  frequent  lavage. 
Keratitis  may  be  superficial  or  ulcerative.  It  may  terminate  in 
perforation,  with  hernia  of  the  iris,  or  the  infection  may  extend  to 
the  deeper  parts,  producing  purulent  disintegration  of  the  eye  and 
final  atrophy. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       129 

Erysipelas  also  may  give  rise  to  le  ion    of  the  eyelid  .  ab  <■•    ■ 
and  even  gangrene,  bul  .'ill  these    ub  ide  very  readily. 

Otitis  tiic(li;i  is  very  rare  in  variola.    Out  of  a  total  "I  755  c 
ending  in  recovery  I  find  il  noted  only  in  ten  instance  ,    Suppuration 
of  the  ear  is  sometimes  observed  in  ery  ipela  .  bul   i      imp] 
involvemenl  of  the  external  ear,  and  is  devoid  of  gravity. 

In  the  majority  of  cases  otitis  occur  al  the  end  of  the  disease  or 
during  convalescence.  The  beginning  i-  marked  by  pain  and 
persistence  or   recurrence  of  fever.     Whether   the   tympanum   is 

opened  spontai usly  or  by  paracentesis,  the  symptoms  subside 

with  satisfactory  rapidity,  and  in  mosl  cases  recovery  i-  obtained 
and  hearing  is  preserved  intact.  Some  patients,  however,  left  the 
hospital  with  a  piirulenl  discharge.  In  -nine  rare  instances  otitis 
gives  rise  to  alarming  manifestations.  One  patienl  exhibited 
meningeal  disturbances  which  rapidly  yielded  to  the  influen©  ol 
bromide.  Three  others,  suffering  from  post-rubeolar  otitis,  de- 
veloped mastoiditis  and  were  transported  to  a  special  hospital. 
Finally,  two  children  died  of  septicemia  as  a  result  of  post-rubeolar 
otitis. 

Apart  from  the  lesions  resulting  from  propagation  or  a  superadded 
infection,  disorders  which  seem  to  be  dependent  upon  some  toxic 
central  lesion  may  sometimes  occur.  Thus,  during  convalescence 
from  the  most  varied  infections,  amaurosis,  optic  neuritis,  deafness 
or  vertigo  due  to  labyrinthine  lesions,  may  occur.  According  to 
my  statistics,  however,  such  manifestations  are  exceptional. 

Cutaneous  Manifestations  in  Infections. 

In  the  course  of  infections  the  nutrition  of  the  skin  is  more  or  as 
profoundly  disturbed.  This  is  clearly  evidenced  by  the  dryness  and 
frequent  desquamation  of  the  integument,  even  in  the  absence  of 
eruptive  fevers,  the  frequency  of  suppurations  and.  in  a  great  number 
of  instances,  the  secondary  disorders  occurring  in  the  adnexae  of  the 
skin — the  loss  of  hair  and  the  trophic  alterations  of  the  nails,  which 
become  brittle  or  fissured.  These  various  manifestations  are  a] 
ciable,  particularly  in  those  infections  which  have  a  certain  duration. 
They  are  most  readily  studied  in  typhoid  fever.  During  convales- 
cence, especially  in  children,  a  furfuraceous  desquamation  of  the 
lateral  regions  of  the  body  occurs. 

In  some  instances  the  cutaneous  infection  is  of  external  origin, 
and   sometimes  appears  alone.     At  other  times  it  occurs  in  connec- 


430  IXFECTIO  US  DISEASES. 

tion  with  an  infection  which,  by  disturbing  the  organism,  has  played 
the  role  of  a  predisposing  cause. 

In  another  group  are  to  be  placed  those  cutaneous  infections 
which,  unlike  the  preceding,  are  of  inward  origin,  and  are  effected 
from  within  outward.  The  same  microbes  are  sometimes  concerned 
in  both  cases,  and  the  symptoms  also  may  be  identical.  The 
mechanism,  however,  is  altogether  different,  and  the  evolution 
follows  a  course  peculiar  to  each  group.  The  cutaneous  lesion  is  the 
result  of  a  discharge  tending  to  throw  out  the  infectious  germs 
which  have  invaded  the  organism.  Not  only  the  figurate  elements, 
but  also  the  soluble  substances  are  thus  eliminated  by  the  skin. 
This  leads  us  to  a  third  group  of  manifestations — i.  e.,  symptoms 
or  complications  of  a  toxic  order  occasioned  by  the  poisons 
which  are  produced  in  the  economy,  and  may  be  compared  with 
similar  manifestations  observed  in  a  great  number  of  exogenic  in- 
toxications. 

Excepting  the  cases  in  which  the  pathogenic  agent  is  directly 
inoculated,  as  occurs  in  tuberculosis,  glanders,  and,  at  times,  with 
the  pyogenic  cocci,  the  apparently  spontaneous  development  of  a 
cutaneous  lesion  is  always  referable  to  some  previous  disorder  in 
the  organism.  There  has  been  an  infection,  some  digestive  disturb- 
ance, or  a  nutritional  disease,  such  as  diabetes.  In  subjects  thus 
predisposed  there  may  often  be  found  some  occasional  cause — 
friction,  slight  traumatism,  biting,  superficial  excoriation,  applica- 
tion of  irritating  substances,  exposure  to  physical  agents,  heat,  light, 
and,  finally,  cold.  While  it  can  no  longer  be  admitted  that  cold  is 
of  itself  sufficient  to  create  erysipelas,  it  is  certain  that  it  singularly 
predisposes  to  it. 

One  remarkable  character  of  cutaneous  infections  is  the  facility 
with  which  they  return;  relapses  and  recidives  are  almost  the  rule. 
Repeated  recurrence  of  furunculosis  and  erysipelas  are  familiar  illus- 
trations of  this  fact.  As  far  as  erysipelas  is  concerned,  it  is  certain 
that  the  infection  is  not  terminated  after  an  apparent  recovery,  if 
certain  vasomotor  disorders  persist.  These  disorders  are  some- 
times transitory  and  sometimes  permanent.  In  the  former  instance, 
a  slight  occasional  cause,  a  movement,  an  emotion,  at  times  simply 
the  exercise  involved  in  speaking,  is  required  in  order  to  cause  the 
face  to  become  scarlet.  In  other  cases  the  patient  retains  a  perma- 
nent red  color.  At  the  end  of  several  weeks  this  color  still  persists. 
The  patient  believes  himself  completely  cured;  as  soon,  however, 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  A  -i    If,       \\>,\ 

as  he  becomes  tired,  or  expo  e    him  elf  bo  cold,  b  new  attack  of 
erysipelas  occurs. 

There  is  another  group  of  infectious  le  ion  ('t  the  kin  which 
already  stated,  are  due  to  microbic  discharge.  Pyodermia 
frequent  in  children,  the  germ  commonly  penetrating  from  without. 
In  certain  cases,  however,  analogous  Lesion*  are  brought  about  by  a 
galactophoritis  of  the  mother:  the  pus  cocci  are  ingested  by  the 
child  with  the  milk,  and  are  subsequently  eliminated  by  the  .'-kin, 
causing  the  development  of  pustules. 

Lesions  produced  by  microbic  elimination  through  the  Bkin  an 
times  erythematous  or  papular.  The  type  U  furnished  by  syphilides. 
The  contagious  character  of  papular  syphilides,  al  leasi  'Alien  they 
are  moist,  leads  to  the  conclusion  (hat  they  represenl  a  Localization 
of  the  morbid  agent.  A  similar  mechanism  has  be<  n  suggested  with 
regard  to  the  lenticular  roseate  patches  of  typhoid  fever.  By 
puncturing  them  Neuhauss  claims  to  have  found  the  bacillu 
Eberth;  the  researches  of  Chantemesse,  however,  have  always  been 
negative. 

The  most  interesting  microbic  eruptions  are  those  of  varicella  and 
variola.  These  differ  clearly  from  each  other  by  their  objective 
characters.  In  varicella  the  eruptive  element  is  constituted  by  an 
oblong  bulla  with  irregular  borders  and  a  clear,  transparent  fluid. 
This  bulla  is  an  elevation  of  the  most  superficial  part  of  the  skin, 
raising  only  the  epidermis.  In  variola,  the  eruption  assumes  the 
.form  of  a  papule,  then  that  of  a  pustule,  which  is  rounded,  hard,  and 
seated  deeply  in  the  skin.  Varicellar  eruption  appears  in  successive 
outbreaks,  so  that  the  most  closely  situated  cutaneous  lesions  are 
of  different  ages;  crusts  are  found  alongside  of  transparent  bulls. 
In  variola  the  lesions  are  of  the  same  age,  at  least  in  the  same 
region;  for  the  eruption  may  already  be  crusty  upon  the  face  and 
hands,  while  it  is  yet  pustular  upon  the  legs.  It  is  also  to  be  re- 
membered that  every  papule  does  not  follow  its  complete  evolution; 
hence,  at  the  end  of  the  disease  the  appearance  is  not  exactly 
similar,  although  all  the  papules  may  have  appeared  simultane- 
ously. 

Exanthemata  of  the  Eruptive  Fevers.  The  study  oi  the  eruptive 
fevers  raises  a  few  problems  of  great  interest  which  cannot  be  solved 
in  a  definitive  maimer  until  the  microbic  agents  producing  them  are 
known.  For  the  time  being  a  few  considerations  may  be  presented 
on  this  subject. 


432  INFECTIOUS  DISEASES. 

The  eruption,  which  is  considered  so  characteristic  of  the  group 
of  eruptive  fevers,  is  not  indispensable.  There  are  on  record  numer- 
ous cases  of  slight  fevers,  of  measles  and  notably  of  scarlatina, 
without  cutaneous  manifestations.  On  the  other  hand,  epidemio- 
logical investigations  have  shown  that  individuals  have  contracted 
scarlatina  from  patients  who  suffered  simply  from  anginas;  on  the 
other  hand,  scarlatinal  patients  have  transmitted  simple  anginas. 
Several  of  our  nurses  attending  scarlatina  patients  have  suffered 
from  sore  throats  without  any  eruption  or  desquamation  whatever. 

In  order  to  explain  these  facts,  several  hypotheses  may  be  ad- 
vanced. These  apparently  non-scarlatinal  anginas  are  either  slight 
scarlatinas,  or  else  a  common  microbe,  the  streptococcus,  exalted  in 
the  throat  of  a  scarlatinal  patient,  may  produce  an  angina  in  other 
individuals.  On  the  other  hand,  the  microbe  of  a  simple  angina 
may  favor  the  development  of  the  scarlatinal  germ.  Finally, 
another  hypothesis  consists  in  considering  scarlatina  as  dependent 
upon  a  streptococcus  which  gives  rise  to  typical  scarlatina  or  to  a 
simple  angina,  as  the  case  may  be. 

If  the  last  theory  is  admitted,  scarlatina  would  accordingly  be 
an  angina  with  erythema.  Several  arguments  may  be  advanced  in 
support  of  this  conception.  Even  leaving  aside  those  arguments 
which  could  be  derived  from  the  etiology,  the  cases  of  simple  anginas 
with  erythema  may  still  be  cited.  These  are  not  cases  of  scarlatina, 
since  the  eruption  has  not  the  same  objective  characters,  no  desqua- 
mation takes  place,  and  the  tongue  is  not  red  and  raw-looking. 
Moreover,  the  eruption  is  contingent,  and  the  skin  does  not  contain 
the  germ  of  the  disease :  the  microbe  is  found  in  the  saliva.  Finally, 
when  the  throat  affection  is  absent,  and  this  is  exceptionally  the 
case,  there  exists  a  microbic  focus  where  the  erythogenic  toxins  are 
elaborated;  it  is  a  cutaneous  or  mucous  membrane  wound,  as  in 
surgical  and  puerperal  scarlatinas.  On  the  other  hand,  bacterio- 
logical investigations  detect  in  the  throat  and,  if  the  patient  dies, 
in  the  blood,  in  case  of  a  complication  occurring  in  the  secondary 
focus,  one  and  the  same  microbe.  This  microbe  is  likewise  found 
in  the  urine  in  case  of  nephritis.  The  microbe  in  question  is  the 
streptococcus,  which  is  held  by  some  to  be  a  common  one;  by  others, 
one  possessed  of  special  characters.  It  is  conceivable  that,  taking 
ground  on  these  facts,  certain  authorities  should  have  considered 
scarlatina  as  a  streptococcic  infection;  a  microbic  focus  is,  in  most 
cases,  developed  in  the  throat,  and  the  toxins  which  are  there  pro- 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  I  ' ■/    If        |.;.; 

duced  give  rise  to  the  erythema,  the  importance  of  the  eruption 
thus  being  reduced  considerably.  Such  is  the  view  advanced  first 
by  Klein,  and  subsequently  well  developed  by  Berge\ 

The  hypothesis  is  seductive.     For  it-  demonstration,  however,  i' 
should  be  established  that  the  organism  of  an  individual  Buffi 
from  or  cured  of  scarlal  inaexerl   a   pedal  influence  upon  th< 
coccus.    The  agglutinating  action  of  the  serum  of  scarlatinal  patients 
should,  for  example,  be  Btudied.    The  Btreptococci  of  scarlatina, 
however,  do  not  occur  muted  in  masses,  and  il  is,  therefore,  difficult 
to  study   their  agglutination.     At    my   suggestion,    Dr.  Courtain 
attempted  to  inject  into  rabbits  the  urine  of  scarlatinal  patients,  and 
noticed  that  at  (lie  end  of  some  time  the  serum  of  these  .'uiirnol- 
acquired  a  certain  protective  power  against   the  streptococc 
scarlatina.    The  experiments  of  the  author,  however,  are  qoI 
sufficiently  numerous  to  render  the  results  conclusive. 

The  same  reasoning  is  applicable  to  measles.  This  disease  is 
especially  contagious  in  the  catarrhal  stage  prior  to  the  appearance 
of  the  eruption.  This  fact  leads  to  the  question  whether  the  pr< 
is  not  an  infection  of  the  nasal  mucous  membrane  giving  rise  second- 
arily to  a  toxic  erythema.  The  researches  of  Dr.  Lesage  seem  to 
confirm  this  view. 

Mechanism  and  Variability  of  Infectious  Erythemata.  The 
frequency  of  erythemata  in  the  course  and  as  a  result  of  the  most 
varied  infections  demonstrates  that  microbic  toxins  exert  a  very 
marked  influence  upon  the  vasomotor  centres.  They  stimulate  the 
vasodilators  and  enable  them  to  react  with  the  greatest  facility. 
I  have  already  referred  to  a  new  proof  of  this  action,  viz.,  the  cutane- 
ous redness  persisting  after  erysipelas. 

This  action  of  infections,  and  notably  of  streptococcic  infections, 
accounts  for  the  curative  influence  exerted  by  some  of  them.  Rebel- 
lious skin  lesions,  ulcers  upon  the  legs,  and  lupuses  have  been  seen 
to  heal  in  consequence  of  an  intercurrent  erysipelas.  On  the  other 
hand,  vasomotor  disturbances  may  awaken  dormant  lesions:  in  one 
case  an  erysipelas  of  the  face  seemed  to  renew  an  eczema  of  the 
hands.  In  a  man,  twenty-three  years  of  age.  erysipelas  provoked 
a  renewal  of  papular  syphilides.  This  man  had  suffered  a  year 
before  from  an  indurated  chancre  and  a  roseola.  The  fresh  cutaneous 
manifestations  yielded  in  a  week  to  specific  treatment. 

The  erythema  of  eruptive  fevers  varies  in  intensity,  sometimes 
without  any  apparent  cause,  sometimes  for  reasons  that  are  readily 

28 


43-4  INFECTIOUS  DISEASES. 

comprehensible.  Thus  in  children  suffering  from  whooping-cough 
the  rubeolar  eruption  is  remarkable  for  its  intensity.  I  had  the 
opportunity  to  observe  two  patients  who  had  been  taking  copaiva 
for  a  few  days  for  gonorrhea,  This  medicine,  which  is  capable  of 
producing  erythemata,  imparted  some  particular  characters  to  the 
eruption  of  an  intercurrent  measles.  One  of  them,  eighteen  years 
of  age,  presented  an  eruption  remarkable  for  the  existence  of  very 
large  patches  of  red  purple  color  on  the  chest,  abdomen,  and  the 
extremities.  The  modification  was  more  profound  in  the  other  case, 
a  young  man  twenty-one  years  old,  who  had  upon  his  face  the 
classical  eruption,  while  upon  the  thorax  the  lesions  were  confluent 
and  intense^  red,  recalling  the  exanthema  of  scarlet  fever;  upon 
the  abdomen,  thighs,  and  arms  were  seen  extensive  slightly  ecchy- 
motic  patches  of  a  livid  red  hue,  disappearing  incompletely  on 
pressure . 

In  some  instances  the  intense  congestion  terminates  in  hemorrhage. 
The  eruption  is  then  slightly  petechial,  though  there  may  be  no  other 
serious  manifestation.  In  certain  cases  of  scarlatina  or  measles  the 
eruption  does  not  disappear  on  pressure;  the  skin  becomes  white, 
but  a  multitude  of  small  red  spots  can  be  seen.  These  minute 
hemorrhages,  even  when  extensive,  have  no  grave  significance. 
Similarly,  in  variola  the  so-called  scarlatiniform  rash,  which  has 
been  well  distinguished  from  true  hemorrhagic  rash,  disappears  only 
in  an  incomplete  manner  on  pressure.  In  more  severe  cases  veritable 
cutaneous  hemorrhages  occur.  They  are  sometimes  more  or  less 
extensive  ecchymoses;  at  other  times,  well  rounded  and  localized 
spots.  These  characterize  a  special  dermatological  type — purpura — 
which  in  some  cases  appears  as  an  isolated  manifestation,  constitut- 
ing infectious  purpura,  and  in  other  instances  as  a  symptom  in  the 
course  of  a  disease,  such  as  measles,  scarlatina,  and  especially  variola. 

Relationship  Between  Intensity  of  the  Eruption  and  Gravity  of 
the  Disease.  Barring  certain  cases  in  which  the  eruption  is  incom- 
plete, others  in  which  the  cutaneous  manifestation  seems  to  subside 
rather  too  soon,  for  instance,  when  the  eruption  of  measles  disappears 
on  the  appearance  of  a  bronchopneumonia,  it  may  be  broadly 
stated  that  the  more  profound  the  infection  the  more  intense  is  the 
exanthema,  We  do  not  say  graver,  since  it  is  hardly  possible  to 
establish  a  perfect  equation  between  the  intensity  and  the  gravity 
of  a  case.  Variola  alone  is  an  exception  to  this  rule.  In  this 
infection  prognosis  is  to  be  based  upon  the  character  of  the  eruption 


INFLUENCE  OF  INFECTIONS  UPON  THE  0BOANI8M. 

rather  than  upon  the  general  phenomena.  We  have  often 
hemorrhagic  variola  occur  in  patients  whose  tate,  al  our  morning 
visit,  seemed  to  be  excellent;  there  wa  no  high  fever,  delirium,  or 
marked  pain;  all  that  could  be  noted  was  a  little  toxic  d]  pnea. 
A  few  hours  later,  dyspnea  was  inten  ified,  and  before  the  end  of  the 
day  the  patient  was  dead,  retaining  con  ciou  qi  -  to  the  la  t.  By 
taking  into  serious  accounl  the  eruption  il  ie  possible  to  ma 
prognosis  which  is  always  verified  by  the  events,  bul  which  astonishes 
(hose  who  have  never  observed  an  epidemic  of  variola. 

In  the  suppurative  forms,  likewise,  the  prognosis  must  be  based 
upon  the  intensity  and  course  of  the  eruption. 

It  is  customary  to  divide  variolas  into  two  varieties:  true  variolas 
and  varioloids,  according  as  the  pustule  evolves  or  aborts.  I'  is 
necessary  to  remark  thai  in  varioloid  the  eruption  does  undergo 
pustulation.  While,  however,  in  variola  the  pustule  ruptures,  and 
an  outward  suppuration  is  produced,  attended  by  secondary  fever, 
in  varioloid  the  pustules  remain  closed.  These  dry  and  are  covered 
with  a  brown  crust;  but  since  they  do  not  run  a  course  of  complete 
evolution,  the  fever  of  suppuration  is  tacking. 

According  to  the  intensity  of  the  eruption,  true  variola  i-  -aid  to 
be  discrete,  coherent,  or  confluent.  The  elements  of  eruption  may 
be  confluent  from  the  first,  or  may  later  become  so  by  fusion  and 
growth.  As,  however,  the  intensity  of  the  eruption  varies  according 
to  the  territories  observed,  it  has  been  agreed  that  the  epithet  must 
be  applied  according  to  the  state  of  the  eruption  upon  the  face. 
At  all  events,  the  eruption  is  generally  abundant  upon  the  face: 
only  those  cases  in  which  a  previous  irritation  has  made  another 
part  of  the  skin  the  point  of  attraction  must  be  excepted. 

It  is  necessary  to  consider  the  condition  of  both  the  skin  and  of  the 
mucous  membranes.  A  profuse  eruption  in  the  throat,  by  embar- 
rassing deglutition,  hinders  alimentation  and  greatly  aggravates 
prognosis.  Not  only  the  number  but  the  evolution  of  the  lesi<  ins  is 
also  to  be  taken  into  account.  If  the  pustules,  even  though  very 
numerous,  remain  well  separated  and.  as  a  result  of  the  swelling  of 
the  skin,  do  not  become  confluent,  recovery  is  probable.  Not  infre- 
quently these  pustules  are  filled  with  a  yellowish  fluid,  grow  and 
assume  an  acne-like  aspect :  this  is  also  a  favorable  symptom.  <  >n 
the  other  hand,  when  there  is  no  edematous  swelling  in  the  face  and 
hands,  when  the  pustules  touch  each  other,  and  particularly  when 
they  fuse,  the  prognosis  is  bad. 


436 


INFECTIO  US  DISEASES. 


At  a  later  stage  of  the  evolution,  if  the  crusts  developing  upon  the 
pustule  are  unctuous  and  yellow,  prognosis  is  favorable.  If,  on  the 
contrary,  the  crusts  become  dry  and  blackish,  prognosis  is  almost 
fatal.  It  is  to.be  noted  in  certain  cases,  even  of  true  variola,  that 
some  pustules  abort;  they  are  prematurely  covered  by  a  blackish 
crust.  The  latter  appearance  assumed  by  certain  isolated  pustules 
should  not  be  confounded  with  the  black  desiccation  of  the  confluent 
elements,  for  premature  desiccation  is  of  good  prognosis ;  it  indicates 
that  the  organism  is  capable  of  struggling,  since  it  is  rapidly  victorious 
at  certain  points.  Lastly,  though  even  secondary  hemorrhages 
aggravate  prognosis,  it  is  well  to  remark  that  sanguinolent  effusions 

Fig.  33. 


Post-erysipelatous  pachydermia. 


occurring  tardily  in  certain  pustules,  notably  in  those  of  the  hands 
and  feet,  are  compatible  with  a  favorable  prognosis. 

Consequences  of  Cutaneous  Infections.  According  to  the  nature 
of  the  process,  the  cutaneous  manifestations  hitherto  described  may 
disappear  without  leaving  any  traces,  or  may  be  followed  by  cicatrices. 
Erythemata,  exudative  inflammations,  even  when  they  have  dis- 
turbed the  cutaneous  nutrition  to  the  extent  of  producing  abundant 
desquamation,  are  completely  cured.  When,  however,  even  simple 
edematous  forms  of  dermatites  are  repeated,  a  certain  degree  of 
pachydermia  may  be  a  sequel.  This  occurs  especially  after  ery- 
sipelas.    In  some  cases  the  lobule  of  the  ear,  in  others  the  face, 


INFLUHNdU  OF  INFECTIONS  UPON  '/'///:  ORGANISM.       |.;7 

remains  thickened.     In  the  case  of  a  little  girl  of  ten  yean  (Fig.  33), 
who  had  several  attacks  of  erysipelas  in  three  years,  developed  | 
erysipelatous  pachydermia  of  the  face.    A    may  I"-  seen  in  the 
figure,  her  cheeks  remained  swollen,  the  upper  lip  protruding,  and 

the  eyelids  were  so  deeply  infiltrated  a    i"  partially  cover  the 
balls.    The  visage  had,  however,  retained  all  h-  mobility  and  the 
child  ;ill  her  intelligence.    This  morbid  state  could,  therefore,  readily 

be  distinguished  from  pachydermia  resulting  from  thyroideal  in- 
competency. 

Without  dwelling  upon  the  vesiculobulbar  infections  and  suppu- 
rative and  gangrenous  lesions  which  are  almosl  invariably  folk 
by  cicatrices,  I  shall  only  remark  thai ,  while  the  eruption-  of  herpes 
evolve  without,  leaving  any  (races,  the  eruption- of  herpes  ZOStei 
terminate  in  cicatrices  remarkable  tor  their  pigmentation  and  the 
sensory  disorders  surrounding  them. 

Clinical  observation  seems  to  demonstrate  thai  the  i>>"ceous 
glands  are  particularly  involved  in  variola.  The  cicatrice-  are 
especially  abundant  and  deep  where  these  glands  are  most  pro- 
fusely distributed,  namely,  upon  the  forehead  and  nose.  In  some 
patients  convalescent  from  grave  variola  we  have  noticed  the 
persistence  of  whitish-yellow  productions  after  the  crusts  had 
dropped  off,  which  are  nothing  else  than  altered  sebaceous  products, 
at  times  simulating  pustules.  They  may  last  for  two  or  three 
months. 

The  Sudoral  Secretion.  Vasomotor  modifications  may  properly 
be  distinguished  from  secretory  changes  on  the  ground  that  while 
cutaneous  congestion  certainly  favors  perspiration,  diaphoresis  may 
often  be  observed  in  conditions  of  vasoconstriction;  the  expression 
"cold  perspiration"  well  indicates  this  peculiar  state. 

Certain  infections  have  the  property  of  diminishing  considerably 
the  sweat  secretion.  The  skin  becomes  dry,  as  is  the  case  in  scar- 
latina and  in  most  of  the  grave  infections.  The  return  of  moisture 
is  a  prognostic  sign  of  importance.  On  the  other  hand,  there  are 
some  infections  diseases  attended  by  such  profuse  sweating  as  to 
constitute  a  source  of  particular  discomfort  for  the  patient.  The 
t}rpe  of  such  infections  is  represented  by  sudor  anglicus,  the  sufferers 
from  which  seem  to  be  plunged  in  a  vapor  bath.  The  same  is 
observed,  though  to  a  less  degree,  in  acute  articular  rheumatism. 
There  are  also  certain  diseases  in  which  the  sweating  occurs,  not 
during  the  entire  course,  as  in  the  preceding  examples,  but  at  a 


438  IXFECTIO  US  DISEASES. 

certain  moment  of  the  evolution  of  the  disease.  Malarial  as  well 
as  symptomatic  intermit  tent  fevers  present  a  stage  of  sweating  at 
the  end  of  each  paroxysm.  Such  is  the  case  in  paroxysms  due  to 
deep-seated  suppurations  and  pyemic  conditions. 

Sweating  may  become  manifest  at  certain  moments  in  the  course 
of  typhoid  fever;  in  general,  however,  patients  do  not  complain 
much  of  perspiration.  Along  with  the  habitual  form  of  typhoid 
may  be  placed  a  sudoral  type,  well  described  by  Jaccoud — from  the 
very  beginning  sudoral  paroxysms  are  observed,  which  recur  during 
the  entire  course  of  the  disease,  and  at  times  persist  during  con- 
valescence. 

Perspiration  is  quite  copious  in  measles  and  discrete  variola,  but 
is  absent  in  grave  cases  of  the  latter  infection.  Finally,  copious 
sweating  is  frequent  in  tuberculosis,  in  which  disease  it  often  appears 
from  the  beginning  of  the  infection,  and  presents  the  peculiar  char- 
acter of  being  produced  during  the  night,  or,  more  exactly,  during 
sleep  and  on  awakening.  It  is  generally  localized  to  the  chest,  and 
annoys  the  patient  considerably;  hence  clinicians  are  now  generally 
agreed  that  it  should  be  combated  by  means  of  antidiaphoretics. 

Cold  perspirations  must  not  be  overlooked.  The  skin  is  cold, 
pale,  sometimes  bluish;  certain  regions,  notably  the  forehead  and 
the  hands,  are  covered  with  a  viscid  perspiration.  This  state  is 
observed  in  cases  of  collapse,  asphyxia,  and  in  the  agonal  stage  of 
all  infections.  It  is  marked  in  choleric  patients  succumbing  in 
collapse  as  well  as  in  diphtheritica  suffocating  by  reason  of  a  laryn- 
geal pseudomembrane. 

We  have  too  little  information  as  to  the  chemical  constitution  of 
sweat  in  the  course  of  diseases  to  know  whether  it  serves  to  eliminate 
toxic  principles.  Such,  however,  seems  to  be  the  fact  in  the  light 
of  investigations  pursued  by  Arloing,  Charrin,  and  Mavrojannis 
concerning  the  toxicity  of  this  secretion.  It  is  further  known  that 
perspiration  may  serve  to  eliminate  bacteria ;  in  the  course  of  septi- 
cemias and  pyemias  sweat  glands  have  more  than  once  been  found 
capable  of  excreting  the  staphylococcus  aureus. 

The  Muscular  System  in  Infections. 

Typhoid  fever  is  the  only  disease  in  which  the  anatomical  modi- 
fications undergone  by  muscles  in  infections  have  been  studied. 
The  muscles  of  individuals  dead  from  typhoid  are  dark  red,  and 
look  dry  and  bloodless  on  section.     Three  varieties  of  degeneration 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  INI    H       !.;:• 

are  detected  under  the  microscope:  granular,  waxy, and  vacuolar, 
which  involve  only  the  contractile  ub  tance,  while  the  nuclei  and 
protoplasm  surrounding  the  latter  proliferate.  Alongside  the  degen- 
erated  fibres,  however,  there  are  found  other*  manifesting  cellular 
regression  well  described  by  KrSsnig  and  by  Durante.  Tin-  i  a 
return  of  the  fibre  to  its  embryonic  tate.  Thi  modification  will 
probably  be  found  in  all  infections,  and  will  confirm  with  reference 
to  the  muscular  tissue  the  law  of  rejuvenation  of  the  organism, 
which  has  already  explained  many  other  modifications  occurring  in 
the  course  of  the  mosl  varied  infections. 

The  muscular  alterations  account   for  the  occurrence  of  partial 
ruptures  and  the  production  of  hemorrhagic  foci  and  even  muscular 
abscesses.     II  is  known,  however,  thai  suppurative  myositis  i 
incident  of  very  rare  occurrence. 

Action  of  the  Colon  Bacillus  Toxins  Upon  Muscular  Contractility. 
It  would  be  interesting  to  inquire  as  to  functional  modifications 
occurring  in  the  course  of  infections  and  first  to  determine  the 
influence  exerted  by  microbic  toxins.  My  researches  on  the  -■ 
tions  of  the  colon  bacillus  elucidated  the  action  of  toxins  upon  the 
nerve  centres  as  well  as  upon  the  muscular  tissue.1  It  will  be  re- 
membered that  the  colon  bacillus  toxin  when  injected  into  ;  _ 
produces  a  poisoning  which  may  be  described  as  follows:  first. 
initial  paresis;  then,  convulsions,  and  finally,  terminal  paralysis. 
Muscular  excitability  is  not  modified  or  is  slightly  increased  < luring 
the  first  period.  At  the  end  of  the  second  period  important  modi- 
fications are  observed:  when  a  series  of  excitations  are  caused  either 
by  acting  directly  upon  the  muscle  or  through  reflex  action — i.  e.. 
by  applying  the  electrodes  at  more  or  less  distant  points  of  the 
organism,  relaxations  follow  contractions  with  remarkable  slow:  ss, 
so  that  these  contractions  very  closely  approach  a  state  of  tetanus. 
This  may  readily  be  seen  by  comparing  the  lines  of  Fig.  34.  The 
first  line  represents  the  normal  contractility  of  the  muscle  under 
the  influence  of  a  faradic  current,  the  others  represent  the  modi- 
fications under  the  influence  of  toxins  administered.  These  lines 
are  analogous  to  those  given  by  fatigued  muscles.  These  experi- 
ments show  that  the  colon  bacillus  secretes  in  bouillon  a  pois 
capable  of  affecting  the  spinal  cord  and  the  muscli —  .  the 
muscular  tissue  itself  or  the  terminations  of  the  motor  nerve. 

1  Roger.     Etude  sur  la  toxicity  des  produits  solubles  du   Bacillus  eoli  communis. 
Archives  de  physiologic.  1893. 


440 


IXFECTIOUS  DISEASES. 


The  foregoing  facts  have  been  confirmed  by  Charrin  and  Miss 
Pompilian.1     These  authors,  experimenting  with  the  pyogenic  and 


Fig.  34. 


1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1  I  I  1 1 


^rrmm-^^^^^t■^m^^^^^^^^^^^h,- 


I  I  H  i1  i' 


Sj- 


"1  I  I  I  L 


Contractility  of  the  normal  (A)  and  of  the  poisoned  muscle  (B  and  C). 

diphtheritic  toxins,  observed  modifications  in  contraction  resembling 
those  produced  by  fatigue. 

Infectious  Osteopathies  and  Arthropathies. 

The  considerations  which  we  have  presented  in  reference  to 
modifications  of  the  bone-marrow  in  the  course  of  infections  explain 
the  development  of  certain  disturbances  and  pains  in  the  limbs  or 
in  the  epiphyses  of  the  joints,  and  account  for  the  rapid  growth 
often  observed  in  young  subjects  during  convalescence.  It  may 
likewise  be  asked  whether  the  lesions  occurring  in  the  course  of 


1  Charrin  and  Mile.  Pompilian.         Influence  des  toxines  microbiennes  sur  la  contrac- 
tion musculaire.     Soc.  de  biologie,  November  28,  1896. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM       \\\ 

gastrointestinal  disorders  play  a  rdle  in  the  production  ol   certain 
lesions  in  youth,  notably  rachitism. 

Dr.  Poncet  has  recently  called  attention  to  a  tubercular  pseudo- 
rheumatism  which  presents  characters  similar  to  those  of  true 
rheumatism.  A  few  years  Bince  I  observed  a  case  of  thk  kind.  I 
was  called  to  sec  a  young  girl,  sixteen  years  of  age,  who  had  Buffered 
for  five  or  six  days  from  violent  pain  in  the  tibiotarsal  joints.  The 
case  had  been  diagnosed  as  acute  articular  rheumatism.  In  fact, 
I  round  the  affected  joints  swollen,  the  skin  white  and  slightly 
edematous,  and  movement  almosl  impossible.  On  a  close] 
animation  I  learned  that  the  patienl  had  emaciated,  and  Ewasstruck 
by  her  facies,  pallor  and  dyspnea.  On  examining  the  thor; 
found  a,  serous  pleurisy  which  had  insidiously  developed.  Then, 
remembering  Unit  the  sister  of  Km  |>:iticn1  had  died  from  acute 
miliary  tuberculosis  two  years  before,  I  attributed  nil  the  presenl 
symptoms  to  tuberculosis.  As  a  matter  of  fact,  the  articular  affec- 
tion was  cured  in  a  week,  the  pleuritic  exudate  was  more  slowly 
absorbed,  but  at  the  same  time  pulmonary  lesions  developed,  ending 
fatally  four  months  later.  It  is,  therefore,  well  to  remember  that 
temporary  tubercular  fluxions  comparable  to  certain  pleurisies  and 
slow  types  of  hydrarthroses  and  white  tumors  may  occur  in  the 
articulations. 

Among  acute  infections  most  frequently  attended  by  articular 
symptoms  scarlatina  occupies  an  important  position.  Few  pati- 
at  least  among  adults,  escape  this  quite  painful  but  not  grave  com- 
plication. A  day  or  two  after  the  eruption,  patients  complain  of 
difficulty  of  moving  the  fingers,  and  it  may  be  seen  that  the  joints 
of  the  phalanges  are  swollen  and  painful.  The  wrist-joint  is  also 
frequently  involved,  but  the  larger  joints  are  rarely,  if  ever,  affected. 
It  is  well  to  add  that  these  arthropathies  are  far  more  frequently 
observed  in  women  than  in  men,  and  are  at  times  accompanied  by 
muscular  pain  and  hj-peresthesia.  In  some  instances  these  com- 
plications appear  during  convalescence,  and  then  present  a  very 
different  localization:  they  affect  especially  the  knee-joint  and  then 
the  shoulders.  Whether  early  or  tardy,  these  arthropathies  behave 
like  those  of  true  rheumatism:  they  do  not  suppurate. 

In  measles  arthropathies  are  rare :  and  the  same  is  true  as  regards 
variola.  In  the  latter  disease  the  affected  joint  may  suppurate, and 
its  history  is  the  same  as  that  of  multiple  suppurations  produced 
bv  this  disease. 


CHAPTER    XV. 

INFLUENCE  OF  INFECTIONS  UPON  THE  VARIOUS  PARTS 
OF  THE  ORGANISM  (Continued). 

Influence  of  Infections  upon  the  Circulator}''  Apparatus.  Functional  Disorders  of  the 
Heart.  Modifications  in  the  Pulse  During  Convalescence.  The  Non-organic  Mur- 
murs. The  Action  of  Microbic  Toxins  upon  the  Heart  and  Blood  Pressure.  Infec- 
tious Myocardites,  Endocardites,  and  Pericardites.  Cardiac  Hypertrophies  in  Rap- 
idly Growing  Young  Subjects.  Action  of  Infections  upon  the  Arteries.  Role  of 
Infections  in  the  Development  of  Arteriosclerosis.  Action  of  Infections  upon  the 
Respiratory  Apparatus.  The  Lungs  in  Infectious  Diseases.  Classification  of  Pul- 
monary Lesions  of  Infectious  Diseases.  Pleural  Lesions  in  Infections.  Serous 
Pleurisies.  Purulent  Pleurisies.  Hemorrhagic  Pleurisies.  Tracheobronchial  Aden- 
opathies.    Remote  Consequences  of  Infections  of  the  Respiratory  Apparatus. 

Influence  of  Infections  upon  the  Circulatory  Apparatus. 

Functional  Disorders  of  the  Heart.  The  action  of  infections  upon 
the  heart  may  be  expressed  by  two  kinds  of  phenomena — functional 
disturbances,  and  lesions.  The  high  temperature  may  be  held 
responsible  for  the  functional  disorders.  In  fact,  when  the  bodily 
temperature  rises,  no  matter  by  what  procedure,  the  pulse  is  accel- 
erated. The  increased  activity  of  combustion  evidently  results  in 
acceleration  of  the  respiratory  movements  and  cardiac  pulsations; 
in  this  manner  elimination  of  the  waste  products  resulting  from  the 
exaggerated  organic  combustion  is  assured. 

Hyperthermia,  however,  does  not  represent  the  onty  factor 
accountable  for  the  accelerated  heart  beats,  since,  if  such  were  the 
case,  the  pulsations  should  always  present  the  same  frequency  at 
the  same  temperature.  It  is  true  that,  in  adults,  each  degree 
centigrade  of  thermal  rise  admittedly  corresponds  to  an  increase  of 
ten  pulsations.  For  instance,  if  the  temperature  rises  to  105.8°  F. 
(41°  C),  the  pulse  rises  from  80  to  120.  Such  is  not  always  the  case, 
however.  Certain  fevers  induce  greater  acceleration  of  heart  beats 
than  others.  For  instance,  in  scarlatina  the  pulse  is  far  more  rapid 
for  the  same  degree  of  temperature  than  in  other  infections.  It  is> 
therefore,  probable  that  toxins  directly  or  indirectly  influence  the 
movements  of  the  heart.  It  is,  moreover,  known  that  an  unusual 
acceleration  in  the  heart  beats  in  the  course  of  an  infection  suggests 


TNFLUENOE  OF  INFECTIONS  UPON  THE  OBOA     /    If.       |  }.; 

some  complication     paralysis  of  the  nerve  centre  .  myocardil 
viscera]  lesion,  a  profuse  hemorrhage,  and,  in  typhoid  fever,  an 
Intestinal  perforation. 

During  convalescence  a  subnormal  temperature  often  coinci 
with  a  pulse  less  rapid  than  normal.  Some  patients,  e  pecially 
children,  may  present  ;ii  this  time  an  irregular  pnl  e.  To  the  un- 
informed physician  this  functional  disorder  maj  a  myocardial 
involvement.  During  the  stationary  period  cardiac  irregularities 
are  of  more  serious  significance, and  should  draw  the  physician's 
attention  to  the  condition  of  the  myocardium.  It  is  to  be  noted, 
however,  that  in  cases  of  erysipelas  with  normal  temperature  or  ;i 
temperature  slightly  above  normal,  whether  the  pulse  is  slow  or 
rapid,  marked  irregularities  in  the  cardiac  movements  may  occur 
at  all  ages  and  even  in  very  benign  cases,  Irregularity  and  inter- 
mittence  of  the  heart  beats  may  also  be  observed  in  cases  of  scar- 
latina; and,  though  they  are  particularly  frequent  during  con- 
valescence, they  may  likewise  be  met  with  during  the  stationary 
period. 

The  absence  of  symptoms  ascribable  to  a  myocardial  lesion  leads 
to  the  admission  that  these  various  manifestations  depend  simply 
upon  nervous  influence. 

Non-organic  Murmurs.  Murmurs  presenting  all  the  characters 
of  extracardiac  murmurs  described  by  Potain  are  very  frequently 
heard  in  the  most  varied  infections.  These  murmurs  are  not  rough ; 
they  are  mesosystolic,  exceptionally  mesodiastolic.  Their  intensity 
varies  from  one  moment  to  another;  the}r  diminish  or  disappear  in 
the  sitting  posture,  and  remain  localized  at  the  points  at  which  they 
originate.  The}^  are  usually  observed  in  scarlatina,  and  are  more 
frequent  in  women  than  in  men.  These  murmurs  are  of  rarer  occur- 
rence in  children ;  they  nevertheless  occur,  and  may  be  heard  even 
in  young  subjects  five  or  six  years  of  age.  Their  frequency  in 
scarlatina  is  about  22  per  cent. 

The  murmurs  of  typhoid  fever  possess  the  particular  character 
of  being  pre-infundibular ;  they  appear  as  early  as  the  end  of  the 
first  week,  which  indicates  that  they  depend,  not  upon  post-infectious 
anemia,  but  upon  the  fever  itself.  Potain  attributed  them  to  febrile 
excitation  of  the  heart.  They  are.  perhaps,  connected  with  a  slight 
degree  of  myocarditis  and,  at  times,  aortitis.  In  support  of  this 
view  I  must  remark  that,  in  certain  instances,  the  extracardiac 
murmur  suddenly  gives  place  to  a  diastolic  '"bruit  de  galop  "  con- 


444  1SFECTI0  US  DISEASES. 

nected  with  myocarditis.  The  excited  state  of  the  myocardium 
explains  the  first  phenomenon;  the  loss  of  tonicity,  supervening 
later,  accounts  for  the  "bruit  de  galop.'"' 

Action  of  Toxins  Upon  the  Heart  and  Blood  Pressure.  Manfredi 
and  Traversa,  experimenting  upon  frogs,  demonstrated  that  the 
soluble  products  of  the  streptococcus  notably  slow  the  movements  of 
the  heart.  Gley  and  Charrin  observed  the  same  effects  with  sterilized 
cultures  of  the  bacillus  pyocyaneus;  they  moreover  obtained  cardiac 
dilatation  in  mammals.  The  latter  manifestation  is  of  considerable 
importance,  since  it  tends  to  indicate  that  the  extracardiac  murmurs 
above  described  may  be  clue  to  a  slight  degree  of  dilatation  of  the 
heart.  I  also  undertook  to  study  the  action  of  the  various  toxins 
upon  the  frog's  heart.1  The  most  interesting  results  were  obtained 
by  means  of  sterilized  cultures  of  the  bacillus  septicus  puditus. 
These  cultures,  when  injected  beneath  the  skin  of  a  frog,  produce 
marked  paresis  within  fifteen  or  twenty  minutes,  excitations  never- 
theless give  rise  to  reflex  movements,  and  the  animal  at  times  jumps. 
If,  however,  under  these  conditions,  the  thorax  is  opened  and  the 
heart  exposed,  this  organ  is  found  to  be  beating  very  slowly  or  at 
a  standstill.  This  arrest  of  the  heart  occurs,  therefore,  at  an  early 
period  of  intoxication,  while  the  other  morbid  manifestations  have 
not  yet  become  grave. 

This  study  was  recently  taken  up  by  Drs.  Chantemesse  and  Lamy2 
who  experimented  upon  the  hearts  of  tortoises  by  means  of  ex- 
tremely ingenious  contrivances.  They  demonstrated  that  the 
typhoid  and  the  diphtheritic  toxins  are  poisons  for  the  myocardium 
and  produce  cardiac  paralysis  after  a  period  of  latency.  Of  still 
greater  interest  is  the  fact  that  the  blood  of  an  animal  which  has 
received  one  or  the  other  of  these  toxins,  exerts  an  exciting  action 
upon  the  heart,  which  action  seems  to  be  due  to  a  new  substance 
elaborated  by  the  organism  under  the  influence  of  the  microbic 
poison. 

These  cardiac  disorders,  however,  do  not  seem  to  be  entirely  due 
to  the  action  of  microbic  poisons  upon  the  heart ;  certain  manifesta- 
tions are  probably  caused  by  an  influence  exerted  upon  the  peripheral 

1  Roger.  Poison  cardiaque  d'origine  microbienne.  Soci^te1  de  biologie,  Jan.  28,  1S93; 
Archives  de  physiologie,  April,  1893.  Action  de  quelques  toxines  microbiennes  sur  le 
cceur.  Society  de  biologie,  Feb.  18,  1893.  Etude  sur  la  toxicite  des  produits  solubles 
du  Bacillus  coli  communis.     Archives  de  physiologie,  July,  1893. 

2  Chantemesse  and  Lamy.  Effets  des  toxines  microbiennes  sur  le  cceur  isol6.  XIII 
Medical  Congress,  section  of  general  pathology,  1901,  p.  137. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  I    /    If        |  ;:, 

circulation.     I'ouclnu-il,  Charrin,  Gamaleia,  ( Hey,  and  Arloing 
dwelt   upon    the    vasomotor    modification*    produced   by   to: 
The  author  studied  fche  influence  of  poison   secreted  by  the  colon 
bacillus  of  dysentery.1    This  microbe  hat  the  advantage  of  furnish- 
ing exceedingly  toxic  cultures.    These  cultures,  when  sterilized  by 
means  of  chloroform  and  injected  into  rabbits  in  the  proportion  of 
().2f)  per  kilogram  of  animal,  cause  death  wil  bin  i  wenty-four  or  forty- 
eight  hours.    The  author  studied,  by  the  graphic  method,  the  el 
produced  upon  (he  ciivulaiion  :ind  respiration.  The  poison  evidently 
I  ended  to  lower  the  blood  pressure.     A  i  ;i  certain  moment,  when  the 
pressure  is  considerably  reduced,  convulsions  occur  which  raise  the 
pressure,  and  slight  improvement  takes  place.     The  morbid  symp- 
toms are  soon  intensified,  the  blood  pressure  continues  to  fall,  the 
descending  course  being  marked  by  renewed  convulsions.     Lastly, 
a  rapid  and  final  reduction  in  pressure  occurs,  and  the  animal  dies. 

These  experiments  show  that  the  heart  struggles  against  the  in- 
fluence of  the  toxin.  Its  contractions  become  more  energetic  and 
slower.  The  poison  does  not,  therefore,  act  upon  the  heart,  and  the 
reduced  pressure  is  probably  due  to  modifications  in  the  abdominal 
circulation.  Intense  congestion  in  the  intestine,  liver,  and  kidneys 
revealed  by  the  necropsy  seems  to  support  this  view. 

Unlike  the  circulation,  respiration  is  but  slightly  disturl  >ed.  When 
2.5  c.mm.  of  the  cultures  are  injected  into  the  veins  the  respiratory 
movements  generally  do  not  present  any  modification.  At  most 
they  may  be  slightly  accelerated  for  a  few  seconds.  With  the 
employment  of  doses  twice  or  three  times  larger  the  movements 
become  136  per  minute,  instead  of  80;  the  amplitude  is  coincidently 
diminished  by  one-third.  These  manifestations  are  transitory,  how- 
ever, and  do  not  last  more  than  fifteen  or  twenty  seconds.  At  a 
more  advanced  stage  of  intoxication  breathing  is  again  acceler- 
ated (Fig.  35);  it  is  then  slowed.  Long  pauses  are  observed:  only 
twenty  or  even  ten  inspirations  per  minute  occur.  The  animal  thus 
succumbs  by  arrest  of  respiration  while  the  heart  is  still  beating. 

Comparison  of  these  experimental  phenomena  with  certain  clinical 
manifestations  reveals  an  analogy — that  is.  lowering  in  the  blood 
pressure.  The  latter  disturbance  has  often  been  attributed  to  diar- 
rhea, which  produces  dehydration  of  the  organism.    Contrary  to  this 

1  Roger.  Les  toxines  du  colibacille  de  la  dysenteric  Annales  de  la  Soc.  de  m£d.  de 
Gand,  April,  1900,  p.  139.  Action  des  toxines  de  colibacille  de  la  dysenteric  sur  la 
circulation  et  la  respiration.     Presse  mod..  Nov.  3.  1900. 


446  ISFECTIO  US  DISEASES. 

view,  I  conclude  from  experimental  results  that  it  is  due  to  intoxi- 
cation, since  the  toxins  do  not  decidedly  affect  the  myocardium. 
"We  now  likewise  understand  why  the  pressure  quickly  rises  as  soon 
as  gastrointestinal  intoxication  is  checked  or  an  intravenous  injection 
of  artificial  serum  is  given  to  remedy  the  effects  of  peripheral  vaso- 
dilatation. Finally,  our  experimental  results  offer  a  new  illustration 
of  the  compensating  antagonism  existing  between  the  peripheral 
and  central  circulation.  By  the  increased  energy  of  its  contractions 
the  heart  endeavors  to  raise  the  blood  pressure,  which  tends  to  fall 
as  a  result  of  abdominal  vasodilatation. 


Fig.  35. 


Rapid  and  short  respiration.  Slow  and  energetic  cardiac  movements.  The  lower  line 
indicates  the  struggle  of  the  heart  against  the  lowering  of  blood  pressure.  The  upper 
line  represents  the  respiration. 

Acute  Myocardites.  Acute  myocardites  may  be  primary,  but 
they  generally  develop  in  the  course  of  an  infectious  disease.  As 
is  the  case  in  other  visceropathies,  localization  in  the  myocardium 
is  favored  by  various  auxiliary  causes.  Among  these,  the  influence 
of  age  is  one  of  the  most  important.  The  affection  is  commonly 
observed  between  the  ages  of  ten  and  thirty  years,  because  at  this 
period  of  life  the  infectious  diseases  capable  of  engendering  it  are 
frequent.  Heredity  also  plays  a  role;  Benecke  found  in  a  total  of 
twenty-eight  cases  twenty-two  presenting  evidences  of  congenital 
debility  of  the  circulatory  system.  Overexertion  has  long  been  con- 
sidered among  the  causes  of  acute,  diffuse  or  circumscribed  myo- 
cardites. Army  physicians  have  often  noted  the  frequent  appear- 
ance of  myocarditis  in  consequence  of  forced  marches.     It  is  at 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  I    /    M.       117 

present  established  thai  overexertion  does  nol  create  alteration  of 
the  myocardium;  it  simply  acts  by  lessening  th<  re  i  tance  of  the 
organism,  and  thus  favors  ii.s  contamination  by  infectiou  germs. 
The  latter  become  localized  in  the  heart,which,  a  a  re  ul1  of  it- 
excessive  activity,  is  found  in  a  state  of  morbid  receptivil 

All  infections,  including  acute  articular  rheumatism,  are  capable 
of  giving  rise  to  acute  myocarditis.  Typhoid  stands  al  the  head  of 
the  list;  all  of  its  forms,  however,  do  nol  equally  predispose  the 
sufferer  to  this  cardiac  involvement.  The  ataxo-adynamic  form 
with  hyperthermia  is  |»;ir!icnl:irly  ap1  to  induce  alteration  of  the 
myocardium.  ( )ut  of  152  necropsies,  Hoffmann  found  bul  54  hearts 
almost  sound.  In  the  course  of  the  third  week  myocarditis  almost 
constantly  makes  its  appearance.  Myocarditis  also  appears  early, 
at  times  on  the  fifth  day  in  grave  confluent  cases  of  variola.  Accord- 
ing to  Desnos  and  Huchard  most  deaths  occurring  befon-  the  eleventh 
day  of  this  disease  must  be  attributed  to  myocarditis. 

Pneumonia,  is  often  complicated  by  myocarditis.  Only  a  few- 
years  ago  French  physicians  received  with  astonishment.  Jurgensen'a 
work,  which  laid  much  stress  upon  pneumonia  myocarditis.  At 
present  pneumonia  is  found  modified;  its  course  is  tedious,  defer- 
vescence is  tardy,  and  fatal  termination  is  more  frequent.  We  are 
now  observing  in  France  what  Jurgensen  observed  in  Germany  a 
few  years  ago:  myocarditis  has  become  one  of  the  frequent  ci 
of  death  in  pneumonia. 

Streptococcic  infections  may  also  be  complicated  by  myocarditis 
This  involvement  is  rare  in  erysipelas,  but  frequent  in  puerperal  and 
surgical  septicemias,  and  may  occur  even  in  streptococcic  - 
throats.  Myocarditis  is  also  encountered  in  scarlatina,  typhus  fever, 
intermittent  fever,  and  acute  tuberculosis.  In  chronic  tuberculosis 
it  seems  to  depend  upon  secondary  infections.  In  measles  it  is 
altogether  exceptional.  Myocarditis  is  of  very  frequent  occurrence 
in  diphtheria,  and  it  is  often  expressed  by  symptoms  difficult  of 
interpretation. 

The  symptomatology  of  acute  myocarditis  is  divided  by  authors 
into  two  phases:  one  of  erethism,  and  another  of  depression.  In 
the  former  stage  the  heart  beats  more  frequently  and  strongly. 
The  patient  complains  of  palpitation  and  precordial  or  sternal  pain 
Pain  may  also  be  caused  by  pressing  the  finger  upon  the  third  or 
fourth  intercostal  space  on  the  left  side,  the  point  which  Peter 
called  "the   precordial  button**  (le  bouton  precordial).     These  dis- 


448  IXFECTIO  US  DISEASES. 

turbances  soon  bring  in  their  train  pulmonary  manifestations, 
notably  intense  dyspnea.  After  three  or  four  days  the  second  phase 
of  myocarditis  appears.  The  heart -beats  become  weak  and  rapid, 
growing  gradually  inappreciable  by  palpation.  On  percussion  pre- 
cordial flatness  is  found  to  be  increased,  owing  to  dilatation  of  the 
heart.  Auscultation  reveals  a  "bruit  de  galop,"  due  to  ventricular 
ectasis  or  a  very  soft  mesosystolic  or  even  systolic  murmur  at  the 
apex.  This  may  be  due  to  functional  incompetence  of  the  auriculo- 
ventricular  valves  as  w^ell  as  to  dilatation  of  the  heart;  hence  the 
disappearance  of  the  murmur  wiien  a  movement  of  the  patient 
increases  the  power  of  the  contractions  by  arousing  the  energy  of 
the  myocardium.  These  phenomena  are  soon  replaced  by  the 
fetal  rhythm  of  Stokes  or  embryocardia  of  Huchard.  The  twro 
murmurs  of  the  heart  are  rapid  and  wreak  and  can  no  longer  be 
distinguished.  They  succeed  each  other  after  the  manner  of  the 
tick-tack  of  a  clock.  Later,  when  the  first  murmur  becomes  so  w7eak 
as  to  indicate  an  incomplete  systole,  and  the  second  murmur  also, 
in  its  turn,  further  diminishes,  a  fatal  termination,  according  to 
Bucquoy,  may  be  expected  within  a  day  or  two.  The  pulse  presents 
modifications  corresponding  to  those  of  the  heart.  It  is  unequal 
rather  than  irregular.  It  manifests  veritable  intermittence  only 
toward  the  end  of  the  disease. 

The  period  of  excitation  is  lacking  in  typhoid  fever.  Myocarditis 
may  even  remain  in  a  state  of  latency  and  be  expressed  simply  by 
acceleration  and  weakness  of  the  heart-beats;  hence  the  occurrence 
of  sudden  death  on  the  occasion  of  movement. 

Differential  diagnosis  between  myocarditis  and  endocarditis  or 
pericarditis  may  sometimes  be  difficult;  an  error  is  more  liable  to 
occur  as  these  various  lesions  may  coexist.  Modifications  in  the 
pulse  must  first  be  taken  into  consideration;  and  then  it  must  be 
remembered  that  the  murmur  of  endocarditis  increases  on  move- 
ment and  under  the  influence  of  any  cause  rendering  the  heart-beats 
more  energetic.  The  reverse  is  the  case  in  myocarditis.  Moreover, 
the  murmur  of  myocarditis  is  transitory.  No  doubt  remains,  how- 
ever, as  to  the  myocarditic  nature  of  the  events  when  the  ' ( bruit  de 
galop"  and  especially  the  fetal  rhythm  are  found. 

Post-infectious  Cardiac  Hypertrophy.  I  believe  that  a  previous 
infection  is  ver}r  often  responsible  for  the  cardiac  hypertrophy  of 
young  subjects  which  is  too  readily  attributed  to  rapid  growth. 
There  are  two  possible  events.     In  some  cases  the  development  of  a 


influence  OF  INFECTIONS  UPON  THE  ORGANISM.       )  \'j 

lesion,  such  as  endocarditis,  is  observed  in  the  course  of  b  di 
At  this  age  (his  lesion  is  curable,  and  a1  the  end  of  o  few  montt 
a  year  or  two  at  the  latest,  h  is  repaired.  The  subjeel  retainc  a 
hypertrophy  of  the  heart,  however,  which  causes  shortness  of  breath 
and  troublesome  palpitations  of  the  heaii  totheextenl  of  rendering 
walking,  bodily,  and  even  intellectual  exertion,  difficult.  If  the 
physician  has  followed  the  entire  evolution,  he  attributes  this  hyper- 
trophy to  the  valvular  lesion,  and  considers  the  case  one  of  compen- 
sating hypertrophy,  somewhal  exceeding  the  requirement*  of  the 
•organism  and  surviving  (lie  causative  lesion.  In  other  instances 
the  heart  does  not  seem  to  have  been  affected  during  the  die* 
no  lesion  of  the  myocardium  has  been  expressed  by  the  slightesl 
murmur.  Hypertrophy,  nevertheless,  develops,  and  when  the 
patient  complains  of  it  and  it  is  discovered,  the  physician  hesitates 
to  connect  the  apparently  recent  disorder  with  the  disease  of  years 
ago.  I  believe,  however,  the  mechanism  to  be  the  same  in  both 
instances.  Infection,  whether  having  affected  the  valvular  endo- 
cardium or  not,  has  produced  lesions  in  the  myocardium.  Compen- 
satory hypertrophy  is  designed  to  re-establish  the  disturbed  cir- 
culatory mechanism;  the  effort,  however,  exceeds  the  end  and 
terminates  in  a  veritable  lesion.  Such  is,  in  my  opinion,  the  cause 
of  a  great  number  of  hypertrophies  attributed  to  rapid  growth  and 
occurring  after  the  most  varied  diseases,  among  which  typhoid  fever, 
acute  articular  rheumatism,  scarlatina,  and  diphtheria  may  particu- 
larly be  mentioned. 

Although  these  hypertrophies  are  at  times  quite  troublesome, 
they  are  not  alwa}rs  grave.  The  heart  which  is  hypertrophied  may 
,soon  cease  to  develop;  the  individual  continues  to  grow,  the  chest 
develops,  and  there  comes  a  time  when  the  heart  appears  to  have 
resumed  a  normal  volume  and  regular  activity.  Only  a  long  period 
■of  time  after,  at  the  end  of  twenty  or  thirty  years,  new  disorders 
become  manifest — i.  e.,  signs  of  chronic  myocarditis,  at  times  accom- 
panied by  valvular  endocarditis,  which  is  developed  in  an  insidious 
manner. 

Endocarditis.  It  is  at  present  well  established  that  every  acute 
endocarditis  is  of  infectious  origin  and  that  all  infections  are  capable 
of  involving  the  endocardium.  Endocarditis  may  be  benign  or 
malignant  and  ulcerative.  These  differences  depend  in  part  upon 
the  nature  and  virulent  potency  of  the  microbe.  The  state  of  the 
attacked   organism,    however,    is    of   greater   importance.     Endo- 

29 


450  INFECTIO  US  DISEASES. 

carditis  assumes  the  ulcerative  character  when  the  individual  is 
already  debilitated  by  previous  or  present  disease,  overexertion,  and 
evil  hygienic  conditions,  abortion,  the  puerperal  state,  or  previous 
lesions,  which  Netter  has  found  in  50  per  cent,  and  Goodhart  in 
75  per  cent,  of  the  cases. 

The  frequency  of  endocarditis  in  rheumatism  was  well  demon- 
strated by  Bouilland.  It  may  be  stated  that  endocarditis  is  the 
rule  in  grave  acute,  generalized  rheumatism;  it  is  exceptional  in 
apyretic,  slight,  and  partial  rheumatism.  The  employment  of  salicy- 
lates, however,  seems  to  diminish  the  cardiac  complication  by  arrest- 
ing the  evolution  of  the  disease.  Endocarditis,  nevertheless  makes 
its  appearance  in  one-fourth  of  the  cases  in  adults.  In  children, 
according  to  Cadet  de  Gassicourt,  it  is  observed  in  the  proportion 
of  80  per  cent.  The  first  symptoms  of  the  cardiac  involvement 
are  generally  manifested  at  the  end  of  the  first  or  in  the  course  of 
the  second  week.  The  lesion  occupies  the  mitral,  less  frequently 
the  aortic,  valves,  and  exceptionally  the  right  heart. 

Other  infections  may  engender  a  vegetative  or  an  ulcerative  endo- 
carditis. It  is  admitted  that  the  lesion  of  the  heart  is  at  times  due 
to  the  action  of  the  principal  agent,  but  in  a  greater  number  of 
instances  it  must  be  attributed  to  secondary  infection.  Endo- 
carditis occurring  in  influenza,  gonorrhea,  and  tuberculosis  results 
from  secondary  infection  by  the  streptococcus,  pneumococcus,  and 
less  often  the  staphylococcus.  It  is  well  to  remember,  however,  that 
Koch's  bacillus  may  be  localized  in  the  endocardium,  especially  in 
cases  of  acute  tuberculosis.  Contrary  to  what  might  be  expected, 
endocarditis  is  very  rare  in  erysipelas;  the  microbe  exhausts  its 
power  in  the  skin  and  manifests  no  tendency  to  invade  the  viscera. 
The  frequency  of  endocarditis  in  pneumonia  has  of  late  been  demon- 
strated by  numerous  observations.  Sometimes  the  streptococcus, 
but  most  frequently  the  pneumococcus,  is  the  responsible  agent. 
The  cardiac  complication  may  occur  in  the  decline  of  the  pulmonary 
infection  or  after  defervescence.  The  aortic  orifice  is  generally  the 
point  of  attack,  and  the  process  is,  as  a  rule,  ulcerative.  Ulcerative 
endocarditis  is  also  encountered  in  37  per  cent,  of  the  cases  of 
pyemias  and  in  11  per  cent,  of  puerperal  septicemias.  Articular 
manifestations  often  accompany  the  process  and  give  it  the  appear- 
ance of  infectious  pseuclorheumatism. 

The  vegetative  or  warty  type   develops  in  an  insidious  manner. 
Some  phenomena,  such  as  precordial  pain,  palpitation  on  the  slightest 


INFLUENCE  OP  INFECTIONS  UPON  THE  ORGANISM.       \:,\ 

exertion,  embarrassed    respiration,  cephalalgi  i   i   the  \ 

bility  of  cardiac  localization.     All  these  manife  tations,  how 
are  inconstant.     Endocarditis,  may  therefore,  readily  escape  notice 
if  the   heart  is  not  systematically  examined.     A.1  the  beginning  of 
valvulitis  the  phenomena  are  those  or  cardiac  excitation;  there  is 
as  yet  no  murmur,  since  al  this  time  the  valve  ft,  thickened, 

;ui(l  incapable  of  vibration  by  the  blood  waves.  The  normal 
murmurs  are  round  to  be  rather  dull;  the  firsl  especially  becomes 
indistinct  at  the  apex  the  swollen  valves  -till  insure  occlusion, bul 
no  longer  snap.  When  the  aorta  \&  the  affected  pari  the  second 
murmur  is  found  dull  a1  the  base.  Only  a1  a  later  period  do  the 
murmurs  of  incompetency  become  manifest. 

The  ulcerative  form  may  also  escape  attention,  bul  for  different 
reasons — the  physician's  al  trillion  is  absorbed  by  the  severity  of 
the  general  phenomena.  In  view  of  these,  two  principal  clinical 
forms  haA^e  been  described:  a  typhoid  form  and  a  pyemic  form 
In  the  former  case  the  pneumococcus  is  the  habitual  agent.  Either 
at  the  beginning  or  four  to  six  days  after  defervescence  of  a  pneu- 
monia the  patient  experiences  a  single  chill  and  rapidly  develops 
fever  at  10-1°  or  105.8°  F.  (40°  or  41°  C).  The  cardiac  pulsations 
are  painful  and  frequent;  the  pulse  is  small  and  often  irregular. 
Adynamia  makes  rapid  progress.  In  some  cases  embolism  occur.-, 
giving  rise  to  sudden  hemiplegia,  exceptionally  to  paraplegia,  at 
which  time  all  doubt  as  to  the  diagnosis  is  dispelled.  In  the  pyemic 
form  the  dominant  feature  is  the  enormous  oscillations  of  the  fever, 
which  occurs  in  the  form  of  paroxysms,  characterized  by  the  three 
classical  stages — chill,  fever,  and  sweating.  This  is  Lancereaux's 
intermittent  form.  In  this  t3^pe  embolism  is  far  more  frequent  than 
in  the  preceding.  In  the  typhoid  type  the  aortic  orifice  is  generally 
affected;  in  the  pyemic,  the  mitral. 

Ulcerative  endocarditis  is  but  exceptionally  curable.  On  the 
other  hand,  the  warty  form  is  often  cured,  and  cured  in  a  complete 
manner.  The  happy  termination  sometimes  occurs  so  rapidly  as 
to  render  the  diagnosis  doubtful.  In  a  case  of  grave  erysipelas  I 
heard  a  systolic  murmur  at  the  apex.  Ulcerative  endocarditis  was 
thought  of,  but  the  murmur  diminished  in  four  days  and  completely 
disappeared  within  a  week.  This  evolution  is  not  rare  when  the 
patients  can  be  watched.  I  treated  a  little  girl  who  suffered  three 
times  from  acute  articular  rheumatism.  During  the  first  attack, 
which  occurred  at  the  age  of  four  years,  mitral  incompetency  was 


452  IXFECTIOUS  DISEASES. 

produced,  which  healed  in  eight  months.  She  had  a  second  attack 
of  rheumatism  when  seven  years  old,  and  developed  the  same 
symptoms,  which  disappeared  as  rapidly  as  in  the  first  instance. 
At  the  age  of  fifteen  years  she  had  a  third  attack,  and  a  systolic 
murmur  again  made  its  appearance,  and  took  eighteen  months  to 
disappear.  From  that  time  on  the  heart  remained  hypertrophied ; 
but  this  condition  was  later  compensated  by  the  mechanism  already 
indicated.  At  present  this  individual  is  nineteen  years  old,  and  the 
heart  seems  to  be  absolutely  normal. 

Pericarditis.  Pericarditis  may  represent  the  principal  localization 
of  an  at  first  generalized  infectious  process,  or  it  may  supevene  as 
a  secondary  phenomenon.  It  often  coexists  with  endocarditis  and 
myocarditis ;  such  a  pancarditis  is  the  rule  in  children.  As  in  the  case 
of  endocarditis,  bad  hygienic  conditions,  fatigue,  alcoholism,  and  cold 
favor  the  localization  in  the  heart.  Thus  is  explained  the  occurrence 
of  epidemics  of  pericarditis  formerly  observed  in  besieged  cities. 

The  pericardiac  lesion  often  occurs  under  the  influence  of  rheu- 
matism. The  eruptive  fevers  may  also  reach  the  pericardium.  At 
the  eruptive  period  of  variola  dry  pericarditis  is  said  to  develop; 
later,  purulent  pericarditis  is  found.  It  is  rare  in  measles,  but  quite 
frequent  in  scarlatina.  In  the  latter  instance  it  is  said  to  easily 
become  purulent  or  hemorrhagic  in  character,  but  my  observations 
do  not  confirm  this  statement.  I  have  mainly  found  dry  peri- 
cardites.  During  the  stationary  period  or  in  convalescence  friction 
murmur  is  heard,  lasting  for  five  or  six  days;  it  seldom  persists  for 
two  weeks.  There  may  be  no  disturbance  to  draw  the  physician's 
attention  to  the  heart,  or  the  patient  may  in  some  cases  complain 
of  palpitation  and  precordial  pains.  The  beginning  of  the  process 
may  be  marked  by  syncope.  In  the  course  of  erysipelas  I  have 
sometimes  heard  pericardial  frictions  which  disappeared  after  causing 
some  pain,  palpitation,  and  tachycardia.  In  two  instances,  however, 
pericarditis  caused  a  fatal  termination.  A  woman,  seventy-two 
years  old,  suffering  from  a  wandering  erysipelas,  died  on  the  eleventh 
day,  and  the  necropsy  revealed  a  purulent  pericarditis  and  a  slight 
mitral  valvulitis.  Another  woman,  eighty-two  years  of  age,  also 
suffering  from  an  attack  of  wandering  erysipelas,  succumbed  when 
the  cutaneous  lesions  were  almost  cured;  at  the  necropsy  a  purulent 
pericarditis  was  found. 

Pericarditis  is  frequently  observed  in  tuberculosis;  14  per  cent,  of 
pericardites  are  connected  with  tuberculosis  (Bamberger). 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  i  VI    v.       );,;; 

In  some  cases  pericarditis  ii  u  hered  in  by  chills,  fever,  dyspnea, 
precordial  pain,  at  timee  by  dysphagia.  The  temperature  usually 
rises,  but  in  certain  cases  il  may  be  lowered  a1  the  moment  of  this 
complication,  as  occurs,  for  example,  in  typhoid  fever  (Charcot, 
Brouardel).  In  the  majority  of  cases  pericarditis  remains  in  a 
of  latency;  daily  examination  i  required  in  order  to  discover  it. 
h-  must,  therefore,  be  systematically  looked  for  in  the  coin 
diseases  capable  of  causing  this  complication. 

The  nature  of  the  effusion  is  of  greal  prognostic  value,  for  it 
indicates  the  degree  of  gravity  of  the  causative  pro©  Prognosis 
is  favorable  in  cases  of  dry  pericarditis;  doubtful  in  cases  with 
effusion;  xcvy  grave  in  purulent,  and  fatal  in  hemorrhagic  peri- 
carditis. When  the  previous  condition  and  age  of  the  patient  at 
well  as  the  etiological  conditions  and  general  Bymptoms  are  further 
taken  into  consideration,  all  the  elements  required  for  a  correct 
appreciation  of  the  case  will  be  at  hand. 

Action  of  Infections  upon  the  Arteries. 

Acute  arteritis  is  not,  as  was  once  believed,  a  generalized  process 
causing  fever,  but  a  localized  affection  resulting  from  fever.  Its 
etiology  may  be  described  by  a  single  word — infection.  The  mosi 
typical  example  is  represented  by  arteritis  of  the  limbs  with  con- 
secutive gangrene  occurring  mainly  in  grave  infections  and  nearly 
always  at  their  decline  or  during  convalescence. 

Typhoid  is  undoubtedly  the  infection  most  frequently  concerned 
in  arteritis.  This  complication  is  usually  observed  in  the  lower 
extremities  on  one  side,  oftener  on  the  right  than  on  the  left,  and 
preferably  in  the  posterior  tibial,  next  the  femoral,  anterior  tibial. 
or  dorsalis  pedis  artery :  the  arteries  of  the  upper  extremities  an  i  less 
frequently  involved:  the  iliac,  external  carotid,'" Sylvian  (Vulpian  . 
even  the  pulmonary  (Hoffmann)  artery.  The  arterioles  of  the 
viscera  are  often  affected  during  the  stationary  period,  while  arteritis 
in  the  limbs  seldom,  if  ever,  appears  before  the  third  week,  and 
sometimes  not  until  the  forty-first  (Rendu),  or  even  fifty-eighth  day 
(Barie). 

According  to  Leyden,  influenza  causes  acute  arteritis  as  often  as 
if  not  more  frequently  than  typhoid  fever  does.  In  half  of  the  cases 
the  popliteal  is  the  seat  of  inflammation:  next  the  femoral,  humeral, 
axillary,  cerebral,  and  central  artery  of  the  retina.  Here  also  the 
complication  occurs  during  convalescence. 


454  IXFECTIO  US  DISEASES. 

Arteritis  has  been  noticed  in  variola,  especially  in  the  hemorrhagic 
form  of  it,  sometimes  as  early  as  in  the  period  of  eruption,  at  other 
times  later,  and,  apart  from  the  aorta,  the  coronary  arteries  are 
usually  attacked.  Scarlatinal  arteritis  also  localizes  in  the  coroll- 
aries, and  is  a  complication  of  rare  occurrence.  In  a  total  of  2213 
cases  observed  in  our  wards  of  Porte  d'Aubervilliers  we  found  only 
one  instance  of  acute  arteritis  in  scarlatina,  and  that  was  seated  in 
the  femoral  artery.  In  measles  it  has  scarcely  ever  been  observed. 
It  is  not  rare  in  diphtheria,  and  involves  usually  the  coronary, 
pulmonary,  renal  and  Sylvian  arteries.  Erysipelas  has  been  seen 
to  be  complicated  by  inflammation  of  the  circle  of  Willis  (Ponfick), 
obliteration  of  the  nutrient  arterioles  of  the  eyeball  (Parinaud),  and 
a  thrombosis  of  the  popliteal  (Schmitt).  Among  other  infections 
we  may  cite  puerperal  fever,  septicemias,  pyemias,  typhus,  pneu- 
monia, cholera,  etc.  I  have  observed  cerebral  arteritis  with  throm- 
bosis and  acute  softening  of  the  brain  in  the  course  of  a  gastro- 
enteritis. Arteritis  of  the  limbs  was  observed  by  Legroux  in  acute 
articular  rheumatism.  Hanot  believes  that  acute  rheumatismal 
arteritis  often  accompanies  endocarditis,  but  remains  unnoticed  by 
reason  of  the  obscurity  of  its  symptomatology.  Leyden  noted  an 
arteritis  of  the  popliteal  occurring  in  a  suppurative  appendicitis. 
We  may  also  mention  the  case  of  Haushalter  concerning  thrombosis 
of  the  Sylvian  and  anterior  cerebral  arteries  in  a  child  suffering 
from  empyema,  and  the  observation  of  Vaquez  regarding  a  tuber- 
cular subject. 

To  sum  up,  while  inflammation  of  the  visceral  arterioles  is  of 
frequent  occurrence  in  infectious  diseases,  acute  arteritis  of  the 
extremities  is  exceptional  outside  typhoid  fever  and  influenza. 

Acute  arterites  may  be  due  to  a  localization  of  the  microbic  agent 
responsible  for  the  principal  disease ;  in  other  cases  they  represent  a 
secondary  infection;  and  in  still  a  third  class  of  instances  toxins, 
independently  of  figurate  elements,  seem  to  be  capable  of  producing 
inflammation  in  the  vessels. 

The  microbes  of  typhoid  fever,  pneumonia,  and  erysipelas  some- 
times induce  arteritis.  On  examining  the  myocardium  in  eight 
typhoid  cases  Rattone  found  Eberth's  bacillus  in  the  walls  of  the 
arterioles  distributed  to  this  muscle  in  seven  instances.  In  almost 
all  cases  in  which  the  arteries  of  the  extremities  are  affected,  inflam- 
mation is  due  to  a  superadded  infection  by  the  pneumococcus,  more 
frequently    by    the    streptococcus.      Finally,    arteritis    sometimes 


INFLUENCE  OF  TNFE0TI0N8  UPON  THE  ORGANISM.      .\:,:t 

develops  under  the  influence  of  toxin  .  a    i    undoubtedly  the  ■ 
in  certain  instances  of  diphtheritic  arteritis.     Experimental  demon- 
strations  have    Fully   corroborated   clinical    observation   on   tl 
points. 

The  first  symptom  of  arteritis  in  the  limbs  is  generally  pain, 
increasing  during  the  night.  Rise  in  the  bodily  temperature  and 
acceleration  of  the  pulse  also  occur.  Coincidently,  or  somewhat 
later,  torpor,  heaviness,  and  formication  are  fell  in  the  affected  limb. 
Pulsation  in  the  diseased  artery  and  its  branches  is  a1  first  weakened, 
and  subsequently  disappears;  ;i  supplementary  circulation,  however, 
is  established  which  insures  nulrilion  of  the  parts^  In  n. 
the  events  proceed  thus:  the  color  of  the  skin  in  the  diseased  segment 
becomes  whitish,  its  temperature  is  lowered,  and  sensibility  dimin- 
ished; hence  a  characteristic  contrast  between  the  superficial  hyper- 
esthesia and  painfulness  in  the  deeper  parts  results.  At  a  later  stage 
patches  of  cyanosis  and  even  purpura  make  their  appearance,  firsl 
at  the  end  of  the  limb — i.  e.,  lingers  or  toes,  announcing  the  immi- 
nence of  sloughing.  The  latter  condition,  however,  does  not  qi 
sarily  occur;  a  sufficient  collateral  circulation  may  tardily  be  effected, 
and  the  limb  then  gradually  resumes  its  normal  characters.  In 
other  instances,  after  a  deceiving  remission,  the  symptoms  again 
become  aggravated,  and  the  affection  runs  its  course  toward  sphace- 
lation. When  gangrene  is  thus  produced  the  danger  is  not  confined 
to  the  limb;  the  toxins  originating  in  the  dying  tissues  induce  a 
very  grave  general  state.  Fever,  fetid  diarrhea,  dyspnea,  delirium, 
and  a  profound  adynamia  are  some  of  the  features  of  the  general 
condition,  in  which  fatal  termination  sometimes  occurs  before  the 
separation  of  the  eschar. 

Role  of  Infections  in  the  Development  of  Arteriosclerosis.  The 
study  of  acute  arteritis  raises  a  pathogenic  problem  of  the  highest 
interest :  What  is  the  role  of  infection  in  the  development  of  arterio- 
sclerosis ? 

In  the  first  place,  I  think  it  is  a  well-demonstrated  fact  that 
gastrointestinal  disturbances  when  characterized  by  excessive 
fermentations  and  putrefactions  induce  arterial  changes.  The 
question  is  one  of  veritable  intoxication  of  the  organism,  and.  though 
the  liver  is  generally  the  organ  most  profoundly  affected,  the  poisons 
sooner  or  later  pass  the  barrier  opposed  by  this  gland  and  exert 
their  action  upon  other  parts  of  the  organism,  notably  upon  the 
arteries  and  the  main  emunctorv.  the  kidnev. 


456  INFECTIOUS  DISEASES. 

The  influence  of  temporary  infections  is  not  as  simple  as  that  of 
intestinal  putrefactions.  Numerous  clinical  observations,  however, 
demonstrate  the  reality  of  this  etiological  factor.  Gueneau  de 
Mussy  claimed  to  have  seen  the  arteries  suffer  a  rapid  fibrous  trans- 
formation in  the  course  of  an  attack  of  rheumatism.  Parrot  noted 
the  development  of  infectious  arteritis  of  the  aorta  in  childhood, 
discovering  atheromatous  points  at  the  root  of  the  coronary  arteries. 
Landouzy  and  Siredey  have  shown  that  arterial  lesions  are  far  more 
extensive  than  was  once  believed,  and  terminate  in  arteriosclerosis. 
It  is  true,  however,  that  in  the  acute  period  arterial  lesions  pre- 
dominate at  certain  points;  the  same  is  true  as  regards  the  chronic 
forms.  The  arterial  system  is  not  affected  throughout  in  the  same 
degree. 

In  this  connection  the  influence  of  chrome  diseases  such  as  malaria, 
syphilis,  and  tuberculosis  is  by  no  means  less  important.  Here  also 
it  is  true  that  the  lesions  produced  by  syphilis  are  circumscribed; 
hence  Lancereaux  and  Heubner  deny  to  this  disease  all  influence 
in  the  production  of  arteriosclerosis.  I  believe  Cornil  is  right  in 
attributing  to  syphilis  certain  cases  of  atheroma  occurring  in  young 
subjects  in  the  absence  of  any  other  appreciable  cause.  The  in- 
fluence of  tuberculosis  seems  more  certain.  The  experiments  of 
Vissman  and  of  Therese  demonstrated  that  intravenous  injection  of 
dead  bacilli  or  of  tuberculin  is  followed  by  diffuse  arterial  alterations. 
On  the  other  hand,  H.  Martin  and  P.  Teissier  have  pointed  out  the 
hardness  of  the  arteries  in  certain  young  tuberculous  subjects  in 
spite  of  lowered  blood  pressure,  which  is  the  rule  in  tuberculosis. 

Action  of  Infections  upon  the  Respiratory  Apparatus. 

Larynx.  The  mucous  membrane  of  the  larynx  may  be  the  seat 
of  catarrhal  manifestations  expressing  the  principal  or  subordinate 
localization  of  an  infectious  process.  At  present  there  is  no  doubt 
as  to  the  microbic  origin  of  laryngites,  which  were  usually  attributed 
to  cold.     The  latter  plays  the  role  of  an  occasional  cause. 

Laryngitis  is  sometimes  one  of  the  manifestations  of  a  general 
infection.  In  measles  the  larynx,  trachea,  and  bronchi  participate 
in  the  catarrhal  process,  which  at  the  same  time  involves  the  mucous 
membrane  of  the  nose  and  eyelids.  During  the  stationary  period 
of  infections  the  larynx  may  be  invaded  by  the  morbid  process. 
This  localization  is  generally  of  little  importance,  but  in  some  cases 
it  may  prove  very  serious.     Thus  in  variola  pustules  may  develop 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  I     /    If.      457 


in  the  larynx  and  induce  edema  of  the  glotti  .  The  re  ill 
growing  dyspnea  necessitating  surgical  intervention.  This  hap- 
pened in  five  of  our  patients,  four  of  them  i  offering  from  confluent, 
one  from  coherent  variola.  In  spite  of  tracheotomy,  these  five 
individuals,  who  were  profoundly  infected,  diedi  Even  varicella, 
which  is  generally  a  benign  disease,  may  be  complicated  by  a  laryn- 
geal eruption  of  a  more  or  less  serious  character. 

Anions  other  infections,   no1    to  mention   diphtheria  which,  of 
of  course,  heads  the  list,  we  find  erysipelas,  which  may  presenl  the 
laryngeal  complication  in  exceptional  in  tances:  influenza,  glaj 
tuberculosis,  syphilis,  ;hkI  leprosy. 

Trachea  and  Bronchi.  Tracheobronchitis  i-  of  very  frequenl 
occurrence  in  the  course  of  infections.  It  may  he  produced  by 
various  microbes,  the  most  specific  as  well  as  the  mos1  common  of 
bacterial  agents.  Marfan  lias  endeavored  to  classify  the  various 
types  of  bronchitis.1  The  following  table,  which  we  borrow  from 
this  author,  gives  a  good  idea  of  the  main  varieties  encountered  and 
of  the  mechanism  governing  their  development: 

Bronchitis  of  influenza. 
Bronchitis  of  whooping-cough. 
Bronchitis  of  measles. 
Bronchitis  of  diphtheria. 
Bronchitis  of  anthrax. 
Specific       .       .        Bronchitis  of  bubonic  plague. 
Bronchitis  of  tuberculosis. 
Bronchitis  of  variola. 
Bronchitis  of  malaria. 
Bronchitis  of  glanders. 
Bronchitis  of  svphilis. 

Cold. 

Previous  specific  bronchitis. 
Chronic     affection     of     the 
lungs,  pleura,  and  medi- 
Originating  astinum. 

on  the  spot.      Inhalation  of  irritating  sub- 
Bronchites  mucous         -       stances. 

membrane       Intoxications, 
altered  by       Chronic  organic  or  diathetic 
affections. 
By  autoin-  Adynamic    conditio:  - 

fection.  phoid  fever,  acute  diseases  of 

long  duration,  each' - 
Spreading  from   the   upper 
respiratory  tracts. 

f  Bronchites 
i  of  gastroin- 
Through  the     I  testinal  ori- 
L  tant  parts     I  blood  current .     gin. 

Bronchites 
by   septice- 
[  mias. 


Non-specific 
(generally  due 
to  pneumococc! 
and  strepto- 
cocci). 


Originating 
I  from  dis- 


Bv  hetero-    f 


Contagion  bv  inhalation. 


1  Marfan.     Maladies    des    bronches 
vol.  vi..  p.  2S4 


j_      infection   (. 

Traite"  de  ni£decine.     2d   edition.  Paris,  190], 


458  INFECTIOUS  DISEASES. 

The  respiratory  tract,  at  least  in  its  upper  parts,  being  inhabited 
by  innumerable  microbes,  the  most  ordinary  causes  which  directly 
or  indirectly  disturb  the  mucous  lining  may  offer  to  common 
bacteria  an  opportunity  to  exert  their  pathogenic  action.  It  is 
readily  conceivable  that  even  when  bronchitis  seems  to  be  of  a 
specific  nature,  as  is  the  case  in  measles,  a  secondary  infection  may 
intervene  to  modif}^  its  course.  The  fact  that  (rubeolic)  bronchitis 
is  an  early  and  constant  accompaniment  of  measles  proves  that  it 
is  due  to  the  specific  parasite  of  the  infection;  it  rapidly  resolves, 
but,  dming  its  short  duration  may  permit  common-place  micro- 
organisms to  assume  an  aggressive  attitude,  and  thus  prolong  the 
bronchial  inflammation,  and,  if  sufficiently  exalted,  give  rise  to 
bronchopneumonia. 

The  same  is  true  as  regards  variola.  Variolar  pustules  may  be 
produced  in  the  bronchi  and  often  become  the  starting  point  of  a 
pseudomembranous  process.  Apart  from  this  specific  bronchitis, 
ordinary  bronchitis  is  often  observed  in  variola,  and  seems  to  be  due 
to  the  pneumococcus ;  such  bronchites  were  very  frequent  during 
the  Paris  epidemic  of  1900.  We  must  also  mention  the  bronchitis 
of  typhoid  fever.  It  is  an  almost  constant  complication,  appearing 
on  the  fourth  or  fifth  clay  and  lasting  until  the  period  of  convalescence 
It  is  generally  attributed  to  common  bacteria  of  the  respiratory 
tract. 

In  most  cases  bronchitis  is  not  of  grave  character;  when  intense, 
however,  it  may  embarass  hematosis  and  cause  troublesome  cough- 
ing. In  weakened  individuals  it  tends  to  become  purulent,  and 
gives  rise  to  a  secretion  which  obstructs  the  respiratory  passages, 
is  with  difficulty  eliminated,  and  induces  secondary  lesions  in  the 
pulmonary  parenchyma,  even  bronchopneumonia.  As  a  result  of 
this  stagnation  of  the  purulent  secretion,  gangrene  in  the  smaller 
bronchial  tubes  may  occur,  owing  to  invasion  of  saprophytes.  This 
however,  is  an  incident  of  rare  occurrence. 

Lastly,  we  may  mention  pseudomembranous  bronchitis  which, 
when  very  extensive,  may  cause  death  by  asphyxia.  This  may 
occur  notably  in  diphtheria,  as  I  have  pointed  out  in  a  previous 
chapter  (p.  177). 

The  Lungs  in  Infectious  Diseases. 

Preliminary  Considerations  of  Normal  Physiology.  Pulmonary 
lesions  are  very  frequent  in  the  course  of  infectious  diseases.     Some 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  INI8M.       ir/i 

disseminated  rales  are  commonly  heard  during  life;  al  the  necri 
parenchymatous  alterations  are  almo  I  alwayt  di  closed,which  are 
spoken  of  as  congestive  phenomena. 

The  in  I  crest  of  pulmonary  le  ion  appear  to  be  more  considerable, 
as  the  lungs  are  charged  with  more  importanl  function-  than  was 
once  believed.  It'  this  organ  had  aothing  else  to  do  than  ensure 
gaseous  exchanges  and  hematosis,  even  then  it  would  be  considered 
of  vital  importance.  In  addition,  however,  i1  play*  a  protective 
role  for  the  entire  organism  against  infect  inn-  and  intoxications.  It- 
action  upon  microbes  has  already  been  described  (pp.  156-159).  Its 
act, ion  upon  poisons  is  hy  no  mean-  less  important,  since  microbes 
act  by  virtue  of  the  toxins  they  secrete.  It  had  long  been  known 
that  the  lung  served  as  an  eniunctory  for  volatile  substances.  The 
offensive  breath  noticed  in  patients  in  the  course  of  infections, 
especially  when  these  are  accompanied  hy  excessive  intestinal  putre- 
factions, suffices  to  demonstrate  the  elimination  hy  the  respiratory 
organs  of  certain  principles — sulphuretted  hydrogen,  methylamer- 
captan,  ammonia,  volatile  bases,  etc.  Modern  researches  have 
further  demonstrated  that  the  lungs  also  act  upon  those  substances 
which  they  do  not  eliminate  by  subjecting  them  to  modifications 
analogous  to  those  accomplished  by  the  liver.  The  importance  of 
this  fact  is  evident,  since  all  soluble  substances,  whatever  their  mode 
of  entrance  may  he,  must  pass  through  the  pulmonary  network 
before  reaching  the  nerve  centres. 

The  action  of  the  lungs  upon  poisons  has  received  experimental 
demonstration.  The  writer  experimented  with  strychnine  sulphate1 
and  ammonium  carbonate;  Boeri  and  Giuranna,2  and  Cafiero3  expe- 
rimented with  twelve  poisons;  in  all  these  cases  the  protective  action 
of  the  lungs  was  more  or  less  marked. 

We  may  safely  conclude  that  the  lungs  act  as  protective  organs 
against  infections  and  intoxications.  It  may  therefore  he  asked 
whether  the  disturbances  observed  in  the  course  of  infections  of  the 
respiratory  apparatus  are  simply  due  to  asphyxia  or  whether  intox- 
ication by  pulmonary  incompetency  occurs  as  in  the  case  of  hepatic 
incompetency. 

1  Roger.     Action  des  organes  sur  la  strychnine.     La  Presse  Medicale.  April  15.  I  -    - 
Action  des  poumon,  sur  quelques  substances  toxiques.     Ibid..  June  7.  lx 

2  G.  Boeri  and  G.  Giuranna.     L'azione  protettiva  del  pulmone.     La  Riforma  niedica, 
Dec.  2  and  3,  1S99.  No.  07. 

3  Cafiero.    Recerche  exp.  sull'  azioue  protettiva  del  pulmone.    Gazetta  degli  ospedali 
■e  delle  cliniche,  1S99,  No.  97. 


460  ISFECTIOUS  DISEASES. 

Respiratory  Disorders.  The  respiratory  manifestations  occurring 
in  The  course  of  infections  may  consist  simply  of  functional  disturb- 
ances of  nervous  origin  or  be  dependent  upon  blood  alterations. 
Certain  paroxysms  of  dyspnea  observed  in  the  beginning  of  scarlatina 
may  be  connected  with  these  nervous  influences.  At  a  more  ad- 
vanced period  changes  in  the  respiratory  rhythm  may  characterize 
certain  grave  nervous  forms  or  indicate  paralysis  of  the  bulbar 
centres,  as  in  diphtheria,  or  express  some  cerebral  or  meningeal 
complication.  Dyspnea  may  also  be  due  to  blood  alteration.  Such 
is  notably  the  case  in  hemorrhagic  variola.  The  panting  respiration 
is  at  times  the  only  symptom  expressing  the  gravity  of  infection. 
In  such  cases,  while  the  condition  of  the  skin  is  serious,  the  general 
state  often  seems  to  be  very  satisfactory,  and  the  consciousness  of 
the  patient  is  so  perfect  as  to  render  it  difficult  for  those  around 
him  to  believe  that  he  will  die  within  a  few  hours. 

Modifications  in  the  respiratory  rhythm,  dyspnea  or  Cheyne- 
Stokes  type  of  breathing,  expressing  a  renal  complication,  are  likewise 
due  to  blood  alteration.  Such,  however,  is  not  always  the  case. 
In  the  course  of  infectious  nephritis  dyspnea  may  often  occur  as  a 
result  of  acute  pulmonary  edema. 

Classification  of  Pulmonary  Lesions  of  Infectious  Origin.  The 
lesions  attacking  the  lungs  may  be  divided  into  three  groups,  accord- 
ing as  the  process  is  one  of  primary  infection,  secondary  localization 
of  a  specific  process,  or  dependent  upon  ordinary  bacteria. 

The  lungs  may  be  the  primary  or  exclusive  seat  of  a  well-deter- 
mined infection.  It  is  to  be  noted  that  while  fibrinous  pneumonia 
manifests,  by  its  clinical  features  and  lesions,  indisputable  autonomy, 
and  seems  to  be  worthy  of  classification  among  specific  infections,, 
it  falls,  in  view  of  its  microbe,  to  the  rank  of  non-specific  infections. 
As  a  matter  of  fact,  the  pneumococcus  is  a  quite  commonplace  agent, 
capable  of  giving  rise  to  very  different  processes,  such  as  bronchitis 
and  bronchopneumonia,  In  fact,  clinical  study  and  anatomico- 
pathological  investigations  have  thrown  down  the  barriers  once 
established  between  lobar  and  lobular  pneumonia.  These  two  pro- 
cesses are  connected  one  with  the  other  by  a  number  of  transitions,, 
so  that  pneumonia  has  somewhat  lost  its  specific  character. 

The  lungs  may  be  attacked  by  a  specific  process  invading  them 
primarily  or  secondarily  in  an  exclusive,  predominant,  or  accessory 
manner.  The  fact  that  the  respiratory  apparatus  freely  communi- 
cates with  the  exterior  explains  the  easy  arrival  of  morbid  germs. 


ini<'i1(ii<:n<ii<:  OF  INFECTIONS  UPO&  THE  ORGANISM.       ]<;\ 

It  is  hardly  necessary  to  mention  the  frequency  of  pulmonary  tuber- 
culosis and  the  possibility  of  primary  infection  of  the  lunge  by  an- 
thrax and  glanders. 

Anatomical  and  functional  modifications  occurring  in  the  lung  in 
tho  course  of  infectious  diseases  are  more  important.  Two  kinds  of 
lesions  develop:  some  resull  from  the  localization  of  the  principal 
agent)  others  depend  upon  an  additional  infection.  Of  late  the 
importance  :unl  lYc<|ii<'iicy  of  secondary  infections  iii  the  lunge  have, 
perhaps,  been  somewhal  exaggerated.  Every  bronchopneumonia 
occurring  in  the  course  of  infections  is  generally  considered  as  a 
superadded  process.  The  primary  disease  is  3upposed  to  play  simply 
a  predisposing  role.  It  is  well  to  remember  thai  the  situation  is  the 
same  as  in  the  case  of  the  throat.  The  greal  number  of  microbes 
present  in  the  upper  parts  of  the  respiratory  apparatus  which,  when 
the  mucous  membrane  is  dried  by  fever,  may  be  carried  down  to  the 
deeper  parts  by  the  air  current,  accounts  for  the  frequency  of  inva- 
sions by  ordinary  microbes.  The  latter,  however,  may  do  no  more 
than  play  a  secondary  role.  An  important  point  must  be  noted  here. 
These  common  microbes,  being  capable  of  developing  more  readily, 
inhibit  the  development  of  others  in  artificial  culture  media;  hence 
the  possibility  of  errors  in  interpretation.  These  considerations  are 
supported  by  the  researches  of  Dr.  Lesage,  who  believes  that  bron- 
chopneumonia of  measles  depends  upon  the  specific  microbe  of  the 
latter  disease.  The  author  has  also  noticed  that  in  variola  the  pul- 
monary foci  at  times  contain  very  few  bacteria,  while,  on  the  other 
hand,  large  numbers  of  the  special  elements  which  seem  to  be  char- 
acteristic of  this  infection  are  present. 

We  are  thus  led  to  the  question  whether  lobular  pneumonias 
alwrays  result  from  propagation  of  the  process  from  the  smaller 
bronchi — i.  e.,  an  infection  spreading  from  the  bronchial  ramifica- 
tions toward  the  alveoli.  Is  it  not  likely  that  the  lesion  is  often 
produced  by  propagation  of  the  process  through  the  bloodvessels? 
The  pathogenic  germs,  on  arriving  through  the  blood  cm-rent  at  the 
capillaries  of  the  lungs,  are  arrested  there  and  give  rise  to  an  inflam- 
matory  process.  In  fact,  when  it  is  remembered  that  some  conges- 
tion or  even  splenization  is  discovered  in  almost  every  necropsy,  the 
endogenic  origin  of  certain  infectious  processes  seems  highly  probable. 

Pulmonary  lesions  may  be  divided  into  six  varieties:  congestion, 
splenization,  lobular  pneumonia,  lobar  pneumonia,  hemorrhage,  and 
gangrene. 


462  INFECTIOUS  DISEASES. 

The  expression  pulmonary  congestion  is  of  too  common  use  to  be 
discarded.  It  is  not,  however,  an  exact  expression.  Necropsy 
always  reveals  more  important  alterations  than  the  term  in  question 
indicates.  What  is  observed  is  not  simply  dilatation  of  the  vessels; 
there  are  exudates  and  serous  effusions  appreciable  by  the  unassisted 
eye.  When  the  parenchyma  is  compressed,  a  frothy  and  aerated 
fluid  comes  out.  A  certain  degree  of  edema  is,  therefore,  added  to 
congestion.  Histological  examination  confirms  this  finding,  and 
chemical  analysis  further  demonstrates  the  presence  of  an  exudate 
in  the  alveoli.  It  is  to  be  remembered,  therefore,  that  some  albu- 
minous effusion,  more  or  less  rich  in  cells,  is  always  found.  Some 
of  the  cells  originate  from  desquamation  of  the  alveoli;  others  repre- 
sent various  leucocytes. 

On  examining  the  lungs  of  individuals  dead  of  infections,  it  is 
often  noted  that  crepitation  is  not  well  marked  at  certain  points, 
particularly  in  the  posterior  and  lower  parts :  the  lung  tissue  presents 
a  red  color,  somewhat  bluish  or  blackish.  This  condition  is  desig- 
nated splenization,  but  the  lesion  is  really  more  pronounced  than 
this  term,  adopted  in  view  of  the  macroscopic  appearance,  indicates. 

Coincident^  with  the  latter  lesion,  foci  of  pneumonia  are  observed. 
This  does  not  mean  that  splenization  represents  the  first  stage  of 
hepatization.  The  process  is  different,  and  splenization  at  many 
points  gives  way  to  hepatization.  The  latter  is  characterized,  as  is 
known,  by  a  transformation  of  the  tissue,  which  becomes  dense,  air- 
less, red  or  gray  in  color,  and,  at  least  when  it  is  red,  resembles  the 
tissue  of  the  liver.  This  hepatization  takes  place  in  two  different 
ways:  Sometimes  it  affects  the  lobules  individually;  at  other  times 
collectively.  This  distinction  is  expressed  by  the  terms  lobular  and 
lobar  pneumonia.  There  is  no  essential  difference  between  the  two 
processes.  The  lesions  considered  in  themselves  may  be  identical: 
they  ma}'-  be  equally  rich  in  cells  and  contain  the  same  amount  of 
fibrin.  In  true  pneumonia,  however,  all  the  parts  of  a  lobe  are 
attacked  simultaneously,  and  all  present  the  same  stage  of  evolution, 
so  that  on  section  we  obtain  a  homogeneous  slice.  In  lobular  pneu- 
monias, even  when  they  are  of  pseudolobar  type,  the  lobules  are 
invaded  one  by  one,  so  that  on  section  we  see  different  appearances : 
the  process  is  more  advanced  in  some  than  in  other  lobules.  More- 
over, since  in  most  cases  all  the  lobules  of  a  lobe  do  not  participate 
in  the  same  process,  the  result  is  a  mixture  of  complex  lesions,  so 
that  by  the  side  of  foci  of  hepatization  or  of  a  nidus  of  broncho- 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      463 

pneumonia,  as  it  is  sometimei  called,  we  may  ee  le  ion    of  another 
order    edema,  splenization,  or  emphysema. 

Lobular  is  far  more  frequenl  than  lobar  pneumonia  in  the  co 
of  infections.  The  latter  may,  however,  occur  in  the  beginnh 
the  most  diverse  diseases.  The  mosl  common  ai  ociation  i-  that  of 
typhoid  and  pneumonia.  These  pneumonias,  appearing  from  the 
star!  of  an  infection,  occur  in  individuals  capable  of  reacting  in  an 
almost  normal  manner,and  generally  run  a  favorable  course,  behav- 
ing like  plain  pneumonias.  The  author  observed  a  case  in  which 
pneumonia  and  scarlel  fever  appeared  simultaneously,  and  the  evo- 
lution ran  its  course  in  a  regular  manner.  Likewise,  during  con- 
valescence pneumonias  are  ofien  benign  and  presenl  nothing  special. 
On  the  contrary,  during  the  stationary  period  pneumonias  po 
special  diaraders:  the  beginning  frequently  escapes  observation ;  the 
crepitant  rale  is  absent  or  does  not  present  the  classical  features: 
small  moist  rales  only  are  heard.  In  other  instances  the  blowing 
murmur  is  observed  from  the  first.  The  reactionary  phenomena  are 
variable.  At  times  dyspnea  or  aggravation  of  the  general  state  of 
the  patient,  as  expressed  by  high  temperature,  dryness  of  tongue,  and 
acceleration  of  the  pulse,  load  to  auscultation  of  the  lungs.  Evolu- 
tion is  sometimes  extremely  rapid:  those  pneumonias  are  capable  of 
killing  in  a  few  hours.  When  life  is  prolonged  the  focus  manifests 
a  tendency  to  spread  and  undergo  purulent  transformation,  and 
invade  the  pleura.  If  the  patient  survives,  resolution  of  the  lesion- 
is  tedious.  In  fatal  cases  necropsy  reveals  hepatization  to  be  less 
dry  and  less  rich  in  fibrin  than  in  cases  of  plain  primary  pneumonia. 

Lobar  and  particularly  lobular  lesions  are  also  liable  to  invasion 
by  saprophytes  and  to  gangrenous  transformation.  It  must  be  recog- 
nized, however,  that  pulmonary  gangrene  has  become  very  rare,  if 
we  except  those  cases  in  which  it  is  due  to  disorders  of  deglutition. 
as  is  observed  in  diphtheritic  paralyses. 

The  last  pulmonary  manifestation  to  be  observed  is  hemorrl 
This  may  occur  in  the  form  of  a  circumscribed  infarct  or  a  diffuse 
infiltration.  The  latter  variety  is  especially  frequent  in  those  infec- 
tions which  produce  important  blood  alterations,  notably  in  hemor- 
rhagic variola.  It  may.  however,  be  encountered  under  other  cir- 
cumstances. At  the  necropsy  of  an  individual  dead  of  a  malignant 
scarlatina  the  author  found  diffuse  hemorrhage  in  both  lungs.  He 
also  observed  intense  congestion  in  the  right  and  diffuse  hemorrhage 
in  the  left  lung  of  a  man  who  died  on  the  fourth  day  of  an  erysipelas 


464 


IXFECTIO  US  DISEASES. 


with  progressive  asphyxia  and  high  temperature.  Circumscribed 
hemorrhagic  foci  may  also  develop  as  an  epiphenomenon  in  a  nidus 
of  bronchopneumonia,  or  they  may  result  from  small  emboli  sent  by 
the  heart  or  vessels,  or,  finally,  by  circumscribed  thromboses. 

Among  these  various  manifestations  lobar  and  lobular  pneumonias 
are  undoubtedly  the  most  frequent.  Their  frequency  varies  accord- 
ing to  the  disease  and  the  age.  The  author's  statistics  show,  in  this 
connection,  that  measles  stands  at  the  head  of  the  list;  next  come 
erysipelas  and  diphtheria;  variola  occupied  the  fourth  position. 
Pulmonary  complications  are  altogether  exceptional  in  scarlatina  and 
varicella. 

The  influence  of  age  may  be  seen  if  all  the  observations  of  the 
author  are  put  together  regardless  of  disease.  The  patients  are 
divided  into  three  groups  with  regard  to  age :  (1)  First  childhood— 
i.  e.,  below  two  years  of  age;  (2)  second  childhood — i.  e.,  from  two 
to  fifteen  years  of  age;  (3)  above  fifteen  years  of  age.  It  is  thus 
found  that  pulmonary  complications  are  thirty  times  less  frequent 
for  the  same  diseases  in  adults  than  in  children  below  two  years  of 
age.     This  can  be  seen  from  the  following  table: 


Cases  with 

Number  of 

Pulmonary 

Fatal 

Percentage. 

Observations. 

Lesions. 

Cases. 

Morbidity. 

Mortality 

First  childhood     .           613 

134 

70 

21.9 

11.4 

Second  childhood            974 

67 

17 

6.9 

1.7 

Adults     .       .       .          6445 

48 

33 

0.7 

0.5 

Total 


8032 


249 


120 


3.1 


1.4 


The  author's  observations  further  show  that  pulmonary  complica- 
tions do  not  occur  with  the  same  frequency,  as  regards  the  age,  in 
the  various  diseases  under  consideration.    Here  is  the  result  of  our 

statistics : 

Classification  of  Infections  in  the  Order  of  Decreasing  Frequency  of 
Pulmonary  Complications. 


First  Childhood. 

Second  Childhood. 

Ad 

ults. 

Measles,         31.0  per 

cent. 

Diphtheria,  22.2 

per  cent. 

Erysipelas, 

6.2  per  cent 

Diphtheria,  2S.5        ' 

Measles,         20.7 

" 

Variola, 

2.3        " 

Scarlatina,     10.7        ' 

Variola,            3.2 

" 

Diphtheria, 

0.9 

Erysipelas,      9.0        ' 

Scarlatina,       1.3 

" 

Measles, 

0.6 

Variola,            9.3        ' 

Erysipelas,      0.0 

" 

Scarlatina, 

0.2 

Varicella,         1-0        ' 

Varicella,         0.0 

" 

Varicella, 

0.0 

When  the  relative  mortality  in  pneumonia  is  examined  an  unex- 
pected fact  is  met  with,  namely,  that  bronchopneumonia  of  measles 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       \r,r, 

is  the  complication  most  often  curable.  Finally,  if  we  consider 
gravity  according  bo  age,  we  see  that,  in  the  majority  of  infections, 
recovery  is  niosi,  frequent  during  second  childhood.  Adults  are  sel- 
dom attacked,  but  when  they  are  theprogno  is  is  very  unfavorable, 
since  the  mortality  varies  from  50  to  75  per  cent.  The  following 
summary  shows  the  facts  in  this  respect: 

i  ■    ,  ■  rUagt  of  '  I 
Pulmonary  /<* 

First  childhood 

Second  child! I 

A. lulls 

Tims  an  adult  attacked  by  bronchopneumonia  ha-  less  chance  of 
recovery  than  a  child  under  two  years  of  ;igc. 

Pleuritic  Lesions  in  Infections.  When  there  is  a  septic  or  non- 
septic  lesion  in  neighboring  parts,  and  notably  the  lungs,  the  pleura 
readily  reacts;  hence  the  frequency  of  pleurisies  in  the  course  of 
various  infections.  Inflammation  in  this  serous  membrane  may  be 
expressed  by  the  production  of  fibrinous  exudate,  thickening,  or 
pseudomembranes.  Dry  pleurisies  represent  a  defensive  process 
which  often  circumscribes  the  pulmonary  lesion  and  in  certain 
instances  prevents  rupture  of  the  lung.  When  inflammation  is 
intense,  effusion  takes  place,  which  effusion  may  be  serous,  purulent, 
putrid,  or  hemorrhagic,  according  to  the  state  of  the  subject  and  the 
nature  of  the  pathogenic  agent. 

Serous  Pleurisies.  Serous  pleurisy  often  develops  in  the  absence  of 
any  appreciable  pulmonary  manifestation.  It  has  long  been  the 
general  belief,  therefore,  that  it  may  be  produced  by  such  common 
causes  as  cold.  Since  the  contributions  of  Landouzy,  Kelsch,  Kiener, 
Chauffard,  and  Gombault,  and  on  clinical  as  well  as  anatomico- 
pathological  and  experimental  grounds,  pleurisies  from  cold  are 
rejected,  and  the  general  opinion  is  that  any  pleurisy  which  cannot 
be  accounted  for  must  be  considered  suspicious,  as  it  is  almost  always 
dependent  upon  tuberculosis.  The  author  says  almost  always,  as  it 
is  conceivable  that  it  may  be  caused  by  some  other  infection  or  by 
a  pulmonary  alteration  escaping  observation.  This  restriction,  how- 
ever, does  not  lessen  the  importance  of  tuberculosis  in  the  genesis 
of  apparently  primary  pleurisies.  The  importance  of  the  pleurisy 
may  be  so  great  as  to  relegate  the  pulmonary  lesion  which  has  caused 
it  to  the  background,  and.  as  the  pleuritic  inflammation  may  resolve 
and  disappear,  the  physician  naturally  hesitates  to  admit  the  tuber- 
cular nature  of  such  a  benign  process.     It  is  even  probable  that 

30 


466  INFECTIOUS  DISEASES. 

serous  pleurisy  represents  a  favorable  reaction  and  promotes  recov- 
ery. The  best  treatment  of  a  diseased  organ  is,  indeed,  to  impose 
upon  it  perfect  rest.  By  compressing  the  lung,  by  preventing  its 
expansion,  by  immobilizing  it  more  or  less  completely,  pleurisy 
diminishes  its  activity,  and  thus  realizes  the  major  indication  dis- 
covered by  therapeutists.  There  is,  therefore,  a  growing  tendency 
to  respect  effusions.  Barring  those  cases  in  which  the  effusion  be- 
comes dangerous  by  reason  of  its  too  great  amount,  puncture  is  to 
be  avoided.  Thoracentesis  is  indicated  at  a  later  period  when  there 
is  reason  to  believe  that  the  acute  tubercular  attack  which  caused  it 
is  overcome.  When  the  exudate  of  serous  pleurisies  is  examined, 
no  microbe  is  generally  detected.  It  may  be  assumed  that  the 
microbes  are  localized  in  the  diseased  membrane  or  that  pleurisy  is 
due  to  the  action  of  toxins  secreted  in  the  pulmonary  foci.  In  some 
instances  examination  of  the  effusion  reveals  the  presence  of  bacteria 
and  even  pyogenics.  As  a  rule,  these  are  few  in  number,  and  the 
fluid  must  be  submitted  to  centrifugation  in  order  to  detect  them. 
Under  these  conditions,  streptococci  may  be  found  which,  being 
probably  attenuated  by  the  germicidal  power  of  the  effusion,  have 
not  been  able  to  give  rise  to  a  suppurative  process. 

Pneumonia  is  admitted  to  be  the  most  frequent  cause  of  serous 
pleurisy.  The  effusion  is  produced  during  the  stationary  period  or 
convalescence.  Acute  articular  rheumatism  is  given  the  second 
place ;  then  come  eruptive  fevers,  typhoid,  influenza,  and  whooping- 
cough.  Serous  pleurisy  has  also  been  observed  in  septicemias,  pye- 
mias,  and  even  in  the  course  of  gonorrhea.  It  may  safely  be  assumed 
that  in  all  such  cases  the  pleural  effusion  is  caused  by  a  pulmonary 
lesion  which  is  too  small  to  be  appreciated  or  is  masked  by  the  pleural 
lesion.  Serous  pleurisy,  however,  is  not  of  frequent  occurrence  in  any 
of  the  infections  above  mentioned,  except  typhoid  fever.  If  reference 
is  made  to  the  author's  statistics,  but  four  cases  of  serous  pleurisy 
are  found.  During  convalescence  from  variola,  measles,  scarlatina, 
and  erysipelas  patients  developed  fever  and  complained  of  pain  in 
the  side.  Auscultation  revealed  the  presence  of  pleural  effusion,  the 
serous  nature  of  which  was  verified  by  an  exploratory  puncture.  In 
all  four  cases  recovery  was  effected  spontaneously  within  ten  days. 
Inoculations  with  these  exudates  was  not  practised;  it  is,  therefore, 
an  open  question  whether  the  effusions  depended  upon  latent  tuber- 
culosis, the  acute  infection  having  played  simply  the  role  of  an  inci- 
dental cause. 


INFLUENCE  OF  INFECTIONS  UPOH  THE  ORG  I  VI    \[.       \i,7 

Purulent  Pleurisies.  After  the  details  given  iii  treating  of  suppura- 
tion (p.  222),  the  author  will  not  dwell  upon  the  hi  tory  of  purulent 
pleurisies.    They  develop  under  the  same  condition    a  pleu- 

risies, and  are  connected  with  these  by  a   erie  of  transitioi 
two  processes  are  nol  distinct.    Although  in  mosi  cases  pleuri 
purulent  from  the  beginning,  it  is  uol  rare  to  Bee  a  primarily  serous 
effusion  become  purulent.    Slight  modification*  in  the  virulence  of 
pathogenic  agents  suffice  to  accounl  for  the  difference*  in  the  pr< 

Purulent  pleurisy  may  occur  in  the  course  of  various  pneumoniae 
and  aggravate  prognosis.  A  certain  amounl  of  pus  is  often  found  in 
the  pleura,  whether  the  case  be  one  of  ordinary  pneumonia  or  i 
ondary  one  complicating  measles,  variola,  or  erysipelas. 

Purulent  pleurisy  as  an  affection  apparently  independent  of  a 
pulmonary  lesion  is  not  of  frequent  occurrence.  The  author  has 
observed  several  such  cases.  One  occurred  in  a  woman  profoundly 
infected  by  gonorrhea;  she  developed  a  seropurulenl  pleurisy  which 
was  spontaneously  cured  in  a  month. 

Hemorrhagic  Pleurisies.  As  gangrenous  and  putrid  pleurisies  have 
already  been  referred  to  (p.  240)  the  author's  intention  is  here  to 
say  a  few  words  with  reference  to  hemorrhagic  pleurisies.  This 
variety  of  effusion  when  not  dependent  upon  cancel-  is  generally  due 
to  rapid  tuberculosis.  It  is  at  times  observed  in  pneumonia  and 
bronchopneumonias;  it  may  occur  in  the  most  varied  infection! 
a  result  of  infectious  infarcts  (Ehrlich),  but  in  the  majority  of  in- 
stances it  is  a  complication  of  typhoid  fever.  The  author  does  not 
refer  to  bloody  effusions  observed  in  hemorrhagic  infections:  these 
are  cases  of  hemothorax,  not  of  pleurisies. 

In  typhoid  fever  the  effusion  may  be  sero-hemorrhagic.  A  similar 
effusion  may  occur  in  pleurisies  of  convalescence.  There  are  also 
pleurisies  with  Eberth's  bacillus  which  appear  independently  of 
typhoid  fever.  The  author  has  reported  such  a  case  studied  in  con- 
junction with  Dr.  Charrin.1  A  similar  case  was  published  by  Kelsch. 
Tracheobronchial  Adenopathies.  The  various  lesions  of  the  respir- 
atory apparatus  readily  influence  the  tracheobronchial  ganglia. 
At  the  necropsy  of  individuals  dead  of  pulmonary  affections,  espe- 
cially in  the  case  of  children,  these  glands  are  found  enlarged,  red.  and 
inflamed.  These  acute  glandular  inflammations  commonly  subside 
with  gratifying  rapidity.    They  persist,  however,  in  certain  install     - 

1  Charrin  and  Roger.     Presence  du  bacille  d'Eberth  dans  un  epanckement  pleural 
hemorrhagique.     Soc.  medieale  des  hdpitaux,  April  17.  1891. 


468  INFECTIOUS  DISEASES. 

and  explain  the  cough  resembling  that  of  whooping-cough  occurring 
consecutively  to  measles,  typhoid  fever,  and  particularly  influenza. 

In  the  absence  of  pulmonary  lesions,  some  infections  may  cause 
hypertrophy  of  the  tracheobronchial  glands.  Whooping-cough  is 
quite  notable  in  this  connection.  It  has  also  been  asserted  that, 
owing  to  lymphatic  anastomoses,  anginas  and  erysipelas  of  the  face 
may  produce  enlargement  of  these  glands. 

Since  the  works  of  Loomis  and  Pizzini  a  new  problem  confronts 
us.  Koch's  bacillus  is  often  found  in  apparently  healthy  tracheo- 
bronchial glands  in  individuals  presenting  no  trace  of  tuberculosis. 
Kalbe  has  verified  this  fact  and  estimates  at  8  per  cent,  the  propor- 
tion of  glands  which,  though  seemingly  sound,  contain  the  bacillus. 
The  tubercle  germ  thus  remains  inoffensive  until  an  intercurrent 
disease  diminishes  the  resistance  of  the  organism.  The  infections 
which  easily  affect  the  bronchial  glands  are  those  most  capable  of 
thus  giving  rise  to  an  attack  of  tuberculosis.  It  is  therefore  readily 
conceivable  that  whooping-cough  and  measles  play  a  notable  role 
in  this  connection. 

Remote  Consequences  of  Infectious  Lesions  of  the  Respiratory 
Apparatus.  As  is  the  case  in  lesions  of  other  parts  of  the  organism, 
so  those  of  the  respiratory  apparatus  may  be  completely  cured. 
When,  however,  the3^  are  profound  or  repeated,  these  lesions  are 
often  followed  by  irremediable  alterations.  Emphysema  of  an  almost 
incurable  character  and  even  splenization  are  often  observed  after  a 
bronchopneumonia.  The  author  is  therefore  inclined  to  refer  to 
lesions  of  early  age  the  pulmonary  emphysema  so  frequently 
observed  in  adult  and  advanced  age. 

As  in  other  parts,  cicatrization  of  lesions  may  give  rise  to  sclerosis. 
When  the  lung  is  involved  in  the  process  the  alveolar  walls  and 
vascular  ramifications  are  thickened.  The  same  lesion  is  observed 
in  the  pleura,  which  becomes  thickened  at  certain  points,  or  its  two 
layers  may  be  adherent  to  each  other.  Finally,  sclerotic  lesions  may 
increase  emphysema  and  at  times  cause  bronchial  dilatations. 

It  is  thus  possible  to  connect  various  chronic  lesions  which  fre- 
quently coexist  and  seem  to  be  the  remote  results  of  changes  arising 
from  infections. 


CHA  I'TKIi     X  V  I. 

INFLUENCE  OF  INFECTIONS  UPON  THE  VARIOUS  PARTS 
OF  Till;  ORGANISM  (Concluded  , 

Buccopharyngeal    Manifestation     in     Mea  lea.      Buccopharyngeal    Manifestation 
Scarlatina.     Buccopharyngeal   Manife  tation     of  Varicella  and   Variola.     Bui 
pharyngeal    Manifestations    in   Various   Infections.     Stomach    Disturbance*    and 
Lesions  of  the  Intestine  in  Infection       Amebic  Dysentery  and  Bacteria 
Cholt'riform  and    I lyscntrriform   lOiitcriles.     Cholerifonn  Gastroenterite    and  - 
sonal  Diarrheas.    Dysenicrilorm  Knterite       [nfluence  of  [nfectious  Di  ea  •     upon 
the  Liver.    General  Characters  of  the  Infected  Liver.    Semiology  of  the  [nf» 
Liver.    Action  "f  Infections  upon  the  Pancreas.     Influence  of  Infections  upon  the 
Kidneys.    Influence  of  Infections  upon  the  Genital  <  'rgans.    Influence  of  In  feet  ions 
upon  Menstrual  ion.    Influence  of  Infections  upon  Pregnancy.    Suckling  by  [nf< 
Women. 

Influence  of  Infections  upon  the  Digestive  Apparatus. 

In  examining  a  patient  the  physician  generally  does  not  overlook 

the  condition  of  the  tongue.  This  inquiry  is  particularly  important 
in  infectious  diseases,  as  it  may  give  diagnostic  and  prognostic  indi- 
cations of  considerable  value.  A  tongue  which  is  excoriated  on  the 
borders  is  a  good  sign  of  typhoid  fever;  an  opaline  or  porcelain 
tongue  is  quite  peculiar  to  influenza;  the  red,  raspberry-like  tongue 
is  observed  especially  in  scarlatina.  From  a  prognostic  standpoint 
the  importance  of  moisture  or  dryness  of  the  tongue  is  well  known. 
When  this  organ  manifests  a  slight  trembling  extending  to  the  lips 
and  rendering  speech  jerky  it  indicates  the  imminence  of  delirium 
tremens. 

Lesions  of  the  mouth  and  throat  are  extremely  frequent  in  the 
course  of  infectious  diseases;  but  their  study  is  difficult,  and  the 
differential  characters  ascribed  to  them  are  not  very  certain.  Even 
bacteriological  examination  is  not  free  from  considerable  difficulties 
and  not  infrequently  leads  to  errors.  In  fact,  the  buccal  cavity  is 
widely  open,  and  even  under  normal  conditions  is  inhabited  by 
multitudes  of  microbes.  Microscopic  examination  and  cultivation 
always  reveal  bacterial  associations  (p.  145\ 

It  has.  however,  been  possible  to  determine  certain  clinical  types 
corresponding  to  a  bacteriological  formula.     In  the  first  place,  diph- 


470  INFECTIOUS  DISEASES. 

theria  is  such  a  type;  then  buccopharyngeal  localizations  of  general 
infectious  diseases:  the  eruptive  fevers,  syphilis,  and  tuberculosis 
give  rise  to  well-determined  buccal  lesions.  In  some  instances  differ- 
entiation is  based  upon  clinical  observation,  and,  therefore,  it  is  pos- 
sible to  doubt  its  value.  Such,  for  instance,  is  the  case  in  scarlatinal 
angina,  which  is  considered  by  some  authorities  as  an  enanthema 
produced  by  the  scarlatinal  virus,  by  others  as  a  common  inflam- 
mation due  to  the  streptococcus.  This  constant  intervention  of  the 
streptococcus  in  all  buccopharyngeal  inflammations  further  compli- 
cates the  question.  Hence,  as  was  indicated  by  Dr.  Lemoine,  when 
the  role  of  this  agent  is  to  be  determined,  it  is  necessary  to  look  for 
it  in  the  deeper  parts  of  the  tissues ;  for  example,  by  puncturing  the 
tonsils,  since  if  one  is  contented  with  buccopharyngeal  exudates, 
one  may  obtain  a  virulent  streptococcus  without  having  any  right 
to  draw  a  conclusion  from  this  experiment.  In  fact,  it  has  been 
demonstrated  that  certain  germs  are  exalted  in  the  course  of  various 
diseases,  which  is  particularly  true  as  regards  the  microbes  of  the 
mouth,  and  notably  the  streptococcus.  We  are  thus  able  to  explain 
certain  facts  which  would  otherwise  appear  very  strange.  For 
example,  the  saliva  of  a  scarlatinal  patient  expelled  into  the  phys- 
ician's face  is  known  to  have  produced  erysipelas.  The  author  has 
observed  a  great  number  of  simple  sore  throats  contracted  by  indi- 
viduals nursing  scarlatina  cases.  Finally,  what  seems  to  be  more 
demonstrative  is  the  fact  that  parents  whose  children  suffered  from 
diphtheria  contracted  at  their  bedsides  erythematous  or  exudative 
anginas  in  which  LoefTler's  bacillus  could  not  be  detected.  This  fact 
suffices  to  show  that  the  diphtheritic  microbe  may  favor  exaltation 
of  the  ordinary  bacteria  which,  in  their  turn,  produce  by  contagion 
sore  throats  among  those  surrounding  the  patient. 

Buccopharyngeal  Manifestations  in  Measles.  In  measles  an  enan- 
thema analogous  to  the  cutaneous  eruption  is  observed  in  the  palate. 
Like  the  latter,  it  appears  in  the  form  of  small  discrete  spots  of  an 
intense  red  color.  Certain  symptoms  observable  in  the  mouth  enable 
the  physician  to  make  an  early  diagnosis.  Such  is  erythematous- 
pultaceous  gingivitis,  to  which  Comby  has  drawn  special  attention : 
a  white  coating,  which  is  formed  of  desquamated  epithelial  cells,  and 
may  readily  be  wiped  out  by  slight  friction,  is  seen  upon  the  gums. 
This  manifestation  is  perfectly  plain;  it  remains  to  be  seen  whether 
it  is  specific.  More  value  is  attached  to  Koplik's  sign,  which  is 
appreciable  as  early  as  the  first  or  second  day  of  invasion,  and  disap- 


IN  FLU  UNCI',  OF  INFECTIONS  UPON  THE  ORGANISM.      171 

pears  when  the  cutaneous  eruption  appears.    The  sign  <■• 
small,  bluish-white,  slightly  elevated  Bpo1  .    urrounded  by  s  red 
circle,  and  varying  in  size  from  I  mm.  to  5  nun.  (0.04  to  o.'2  incl 
and  in  number  from  five  to  twenty.    These  appear  upon  the  mu< 
membrane  of  the  lips,  tongue,  and  inner  surface  of  the  cheeke  betv 
the  labial  commissure  and  the  opening  of  Stenon'   <\u<-\.    These  pro- 
ductions are  formed  of  fatty  epithelial  cell  ,  re  i  I  friction,  bu1  can 
be  removed  by  means  of  forceps. 

These  various  manifestations  should  qo1  be  mistaken  \'<>v  inflam- 
matory processes;  they  are  simple  enanthemata. 

Among  buccal  manifestations  we  musl  note  angina,  which  mi 
observed  during  the  invasion  of  measles.     It  is  a  complication  of 
exceptional  occurrences,  at  least  in  adults.     It  may  also  be  oba 
during  convalescence.    The  author  has  observed  twenty-six  such 
cases.     It  is  generally  an  erythematous,  seldom  a  pultaceous,  angina. 

Buccopharyngeal  Manifestations  in  Scarlatina.  As  is  known,  buc- 
copharyngeal manifestations  arc  far  more  frequenl  in  scarlatina  than 
inmeasles.  The  angina  is  the  initial  phenomenon,  and  is  never  absent. 
There  are  two  principal  hypotheses  as  to  its  nature:  the  buccophar- 
yngeal symptoms  may  be  considered  as  a  simple  enanthema,  or  it 
may  be  held  to  be  a  true  angina  due  to  the  microbe  of  scarlatina. 
To  the  former  opinion  it  may  be  objected  that  the  inflammatory 
phenomena  are  too  intense  and  that,  while  a  patient  suffering  from 
measles  does  not  say  anything  regarding  his  throat,  a  scarlatinal 
patient  first  complains  of  pain  in  deglutition.  This  objection  can 
readily  be  answered  by  the  statement  that  scarlatinal  enanthema  is 
more  intense;  the  difference  is  one  of  degree,  not  of  nature.  It  pro- 
duces alteration  in  the  epithelium,  and  thus  permits  buccal  germs  to 
cause  further  injury  in  the  mucous  membrane.  It  is  also  to  be  noted 
that  in  certain  cases  of  scarlatina  angina  is  mild  and  the  patient 
suffers  little;  there  are  a  great  many  intermediate  degrees  between 
the  mildest  and  the  severest  manifestations. 

The  other  parts  of  the  mouth  are  little  affected,  except  the  tongue, 
which  is  involved  in  the  eruptive  process.  From  the  third  to  the 
sixth  day  the  epithelium  of  the  tongue  is  desquamated,  and  the  organ 
assumes  a  characteristic  appearance  comparable  to  that  of  a  straw- 
berry. It  is  not  a  glossitis,  since  the  patient  does  not  experience  any 
pain  or  any  functional  trouble.  It  is  simply  a  process  of  desquama- 
tion similar  to  that  of  the  skin,  and  its  early  occurrence  in  the  tongue 
is  explained  by  the  moisture  of  the  region. 


472  IXFECTIO  US  DISEASES. 

The  greater  intensity  of  the  scarlatinal  exanthema  explains  the 
frequency  of  secondary  buccopharyngeal  infections.  The  buccal 
streptococcus  is  exalted  and  produces  various  alterations  which 
appear  simultaneously  with  the  specific  angina,  or  a  few  days  later, 
and  at  times  only  during  convalescence. 

In  scarlatina,  as  in  measles,  angina  may  assume  a  gangrenous  char- 
acter. This  evolution  occurred  in  two  of  the  author's  cases — chil- 
dren; one  of  them  thirteen  months  and  the  other  three  months  old, 
and  both  succumbed.  The  uvula  and  tonsils  were  completely  sphace- 
lated in  both  instances.  Cultivation  from  the  lesions  revealed  the 
presence  of  streptococcus,  staphylococcus,  and  a  non-virulent  anae- 
robic microbe. 

Buccopharyngeal  Manifestations  of  Varicella  and  Variola.  Vari- 
cella and  variola  may  also  give  rise  to  buccopharyngeal  phenomena. 
Here,  however,  the  question  is  not  one  of  erythema;  vesicles  and 
pustules  appear  just  as  in  the  skin.  The  eruption  is  generally  scanty 
in  varicella,  and  is  produced  in  all  parts  of  the  mouth  without  dis- 
tinction— cheeks,  palate,  tongue,  and  gums.  Variolar  eruption  is  of 
greater  importance.  It  sometimes  appears  early,  and  may  then  serve 
as  a  diagnostic  guide.  When  it  appears  at  the  same  time  as  the 
cutaneous  eruption  it  evolves  more  rapidly,  and  thus,  in  doubtful 
cases,  when  the  diagnosis  between  measles  and  variola  is  undecided, 
examination  of  the  throat  removes  all  doubt:  papules  and  vesico- 
pustules  are  seen  occupying  the  palate,  uvula,  pillars,  gum,  tongue, 
and  cheeks.  This  eruption  is  very  copious  in  coherent  and  confluent 
variolas  and  causes  dysphagia  from  the  sixth  or  seventh  day ;  it  may 
then  aggravate  prognosis  considerably  by  disturbing  alimentation.1 

Buccopharyngeal  Manifestations  in  Various  Infections.  We 
might  review  all  infectious  diseases,  since  all  may  affect  the  buccal 
cavity.  Angina  is  frequently  observed  in  typhoid  fever,  in  which 
its  appearance  is  quite  variable,  being  sometimes  pultaceous,  at  times 
ulcerative,  and  in  other  instances  gangrenous.  It  is  'generally  ad- 
mitted that  erysipelas  frequently  begins  with  throat  symptoms. 
This  classical  opinion  seems  to  the  author  inexact.  It  must  be  due 
to  the  fact  that  patients  generally  speak  of  sore  throat  when  they 
suffer  from  painful  enlargement  of  the  lymphatic  glands  often  accom- 
panying the  cutaneous  lesions,  and  sometimes  preceding  them  by  a 
day  or  two.     In  two  instances  they  existed  four  days  before  the 

1  Coste.  Quelques  considerations  sur  le  diagnostic,  le  pronostic  et  le  traitement  de 
la  variole.     Marseille  m£d.,  January,  1898. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      M .', 

appearance  of  erysipelas.     In    om<    ca  e  ,  bowe1 1 
angina  does  occur.     In  twenty  of  the  author'  il  announced 

fche  onset  of  the  disease.     In  a  youth  of  fifteen  year   ol  age  erysipe- 
latous inflammation  started  from  the  tongue,  which  was  highly 
swollen  and  very  painful  and  presented  a  couple  of  bullae  which 
opened  and  gave  issue  to  a  sanguinolenl  discharge. 

Stomach. 

Numerous  observations  have  proved  the  involvemenl  of  the  stom- 
ach in  infectious  processes.    The  gastric  disturbances  may  theoreti- 
cally be  classed  in  lour  groups  according  as  they  are  of  nervi 
muscular,  chemical,  or  microbic  origin.      Unfortunately,  accurate 
investigations  are  lacking  and  are  very  difficult.    Gastric  chemism 
can  hardly  be  studied  in  the  course  of  acute  infections.     In  view, 
however,  of  the  coated  condition  of  the  mouth,  the  disgust  i 
rienced  by  patients  for  food,  and  frequent  vomiting  of  undigi 
aliments  it  may  safely  be  assumed  that  the  digestive  secretions  no 
longer  possess  their  normal  characters.    At  any  rate,  i1  is  in  n< 
to  be  wondered  at  that  gastric  secretion  is  also  disturbed  when  all 
the  other  secretions  are.     Moreover,  chronic  gastritis  so  often  follows 
the  evolution  of  acute  diseases  that  it  seems  perfectly  rational  to 
assume  a  causal  relation  between  the  two  processes. 

As  in  many  other  visceral  disturbances,  vomiting  is  often  of  nervous 
origin.  We  refer  particularly  to  vomiting  at  the  onset  of  infections. 
It  occurs  soon  after  the  initial  chill,  and  accompanies  the  first  symp- 
toms. At  this  stage  of  evolution  gastric  alterations  cannot  be  sup- 
posed to  have  taken  place,  and,  in  fact,  the  vomiting  is  a  transitory 
incident.  It  is  often  observed  in  the  beginning  of  scarlatina,  measles, 
and  erysipelas.  In  the  latter  disease  it  sometimes  represents  the 
first  symptom  of  a  relapse.  Special  mention  must  be  made  of  the 
initial  vomiting  in  variola,  occurring  for  twenty-four  or  forty- 
eight  hours  coincidently  with  extremely  intense  pain  in  the  epigas- 
trium; its  diagnostic  value  is  no  less  important  than  that  of  rachi- 
algia. 

Vomiting  during  the  stationary  period  and  convalescence  exj  :  - 
on  the  contrary,  gastric  alteration.  Hence  they  are  more  persistent 
and  have  an  unfavorable  prognostic  significance.  It  is  to  be  acknowl- 
edged, however,  that  they  are  not  very  frequently  observed,  and  it 
is  surprising  to  see  patients  overcome  their  dislike  for  nourishment 
and  digest  their  food  so  well.     It  has  thus  been  possible  to  feed 


474  /  v/  I:< ' TJ OUS  DISEASES. 

typhoid  cases.  In  the  author's  wards  variolar  patients  receive  rela- 
tively abundant  nourishment  without  any  inconvenience. 

Observations  by  Kalmus,  Hayem,  Lion,  and  others  demonstrate 
the  possibility  of  an  invasion  of  the  gastric  glands  by  microbes.  Gas- 
tric ulcerations  of  typhoid  fever  have  long  been  known.  Dieulafoy's 
observations  proved  the  gastric  localization  of  the  pneumococcus. 
The  same  observer  has  called  attention  to  heinatemesis  occurring 
in  the  course  or  at  the  end  of  an  appendicitis  or  internal  strangu- 
lation. Having  in  several  instances  opened  the  stomach  of  indi- 
viduals dead  of  variola,  the  author  has  sometimes  found  erosions 
which  are  at  times  quite  profound.  Diffuse  bloody  infiltration  with 
numerous  ulcerations  may  be  found  in  cases  of  hemorrhagic  variola, 
explaining  the  occurrence  of  hematemesis  during  life. 

These  facts,  which  enable  us  to  understand  the  mechanism  of 
acute  gastric  phenomena  in  the  course  of  infections,  may  be  cited  in 
support  of  the  opinion  that  chronic  ulcerations,  notably  simple  ulcers, 
are  of  microbic  origin.  The  process  is  less  intense  and  more  slow 
than  in  the  case  of  acute  disorders,  and  the  lesion  insidiously  formed 
gives  rise  to  symptoms  long  after  the  termination  of  the  infectious 
malady  of  which  it  is  a  remote  consequence. 

Primary  or  predominant  attacks  by  general  specific  infections  are 
rarer  in  the  stomach  than  in  other  organs.  Anthrax,  tuberculosis, 
and  syphilis  of  the  stomach  are  but  exceptionally  observed.  In  rare 
cases  phlegmonous  gastritis  may  occur  as  a  primary  or  a  secondary 
manifestation  in  pyemia,  and,  according  to  observations  of  Ziegler, 
Mintz,  and  Derbek,  seems  to  be  due  to  the  streptococcus. 

Disturbances  and  Lesions  of  the  Intestine  in  Infections. 

Almost  all  infectious  diseases  produce  intestinal  disturbances.  The 
latter,  like  those  of  the  stomach,  may  be  of  nervous,  muscular, 
chemical,  or  bacterial  origin.  The  influence  of  bacterial  action  is 
considerable ;  numerous  researches  have  demonstrated  that  intestinal 
microbes,  notably  the  colon  bacillus,  become  virulent  in  the  course 
of  infections.  This  fact  has  a  double  interest.  When  a  highly  viru- 
lent bacillus  is  found  in  the  intestine  the  disturbances  observed  may 
be  erroneously  attributed  to  its  action.  On  the  other  hand,  the 
increased  activity  of  the  intestinal  germs  accounts  for  certain  local 
symptoms,  such  as  tympanites— perhaps  favored  by  temporary 
atony  of  the  muscular  fibers— diarrhea,  and  even  certain  general 
manifestations,  some  kind  of  secondary  digestive  autointoxication. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  I  VI    H        176 

This  constant  participation  of  the  inte  tine  in  infectiom  proa 
explains  the  developmenl  of  chronic  condition  :  some  individuals 
continue  to  suffer  from  certain  intestinal  disorders,  notably  from  a 
tendency  to  diarrhea,  on  the  slightesl  dietetic  error  or  cold;  others 
suffer  from  rebellious  con  tipation.  The  author  has  observed  several 
instances  of  mucomembranous  enteritis. 

\V'(.  are  thus  led  to  the  question  whether  or  no1  infections  play  a 
r61e  in  the  developmenl  of  appendicitis.    This  thi  aus- 

ible.   The  frequency  of  follicular  lesions  of  the  intestine  give  i1 
support,  but  facts  hardly  respond  to  whal  is  expected.    Only  once 
in  our  wards  has  the  author  seen  appendicitis  follow  measles.    On  the 
other  hand,  having  examined  a  certain  number  of  appendices  al  the 
necropsy  of  individuals  dead  of  various  infections,  particularly  vari- 
ola, the  author  has  detected  no  lesions.     The  importance  of  ' 
negative  results  should  not  be  exaggerated,  however.    More  numer- 
ous investigations  are  required  in  order  to  determine  the  valu 
the  theory  which  is  perfectly  consonant  with  the  data  of  general 
pathology. 

As  already  stated,  intestinal  functions  seldom  remain  regular  in 
the  course  of  infectious  diseases.  Sometimes  constipation  predom- 
inates, as  is  the  case  in  erysipelas;  at  other  times,  diarrhea  which,  by 
reason  of  its  too  great  severity,  may  prove  fatal.  Some  authors  have 
described  an  intestinal  form  of  scarlatina  characterized  by  profuse 
and  incessant  evacuations.  As  a  rule,  intense  and  generally  bilious 
diarrhea  is  observed  in  the  beginning  of  measles;  it  seems  to  In- 
dependent upon  an  intestinal  enanthema.  At  a  more  advanced 
period  choleriform  or  dysenteriform  diarrheas  may  appear  which, 
next  to  bronchopneumonia,  represent  the  gravest  complications  of 
the  disease.  This  complication  is  particularly  dangerous  in  the  case 
of  children.  The  author  has,  nevertheless,  observed  the  case  of  an 
adult  who,  at  the  end  of  measles,  succumbed  to  putrid  pleurisy  of 
intestinal  origin. 

Even  in  a  benign  disease,  such  as  varicella,  intestinal  disorders 
may  prove  fatal  in  young  children.  It  is,  however,  in  variola  that 
this  complication  is  of  particular  importance.  Trousseau  laid  stress 
upon  the  diarrhea  of  the  invasion  period,  which  ceases  as  soon  as 
the  eruption  appears.  While  constipation  is  the  rule  in  slight  cases 
during  the  stationary  period,  diarrhea  renders  the  prognosis  unfav- 
orable in  serious  cases.  It  is  a  fetid  and  profuse  diarrhea,  resisting 
most  medicaments,  and  is  hardly  checked  by  astringents  and  notably 


476  INFECTIO  US  DISEASES. 

by  preparations  containing  tannin.  In  hemorrhagic  variola  bloody 
stools  are  frequent.  In  certain  cases,  especially  toward  the  end  of 
the  stationary  period,  the  stools  may  contain  a  certain  amount  of 
blood:  this  is  a  complication  of  importance,  but  does  not  render  prog- 
nosis particularly  bad.  In  fact,  the  author's  observations  show  that 
of  all  visceral  hemorrhages  enterorrhagia,  when  alone,  is  the  least 
grave. 

It  is  not  necessary  to  describe  the  intestinal  localizations  of  specific 
diseases.  As  in  the  case  of  the  stomach,  localization  of  anthrax, 
tuberculosis,  syphilis,  and  actinomycosis  may  also  occur  in  the  intes- 
tine. Tuberculosis  of  the  stomach  is  an  event  of  very  rare  occur- 
rence, while  it  is  quite  frequent  in  the  intestine,  where  it  may  assume 
the  most  varied  forms. 

Amebic  Dysentery  and  Bacterial  Dysentery.  In  the  classification 
of  infectious  diseases  (pp.  24-30)  it  was  stated  that  two  principal  in- 
fections localize  themselves  in  the  alimentary  canal,  viz.,  cholera  and 
dysentery.  Typhoid  fever,  when  classed  with  septicemias,  might 
also  be  included  in  this  group;  leaving  it  aside,  however,  the  author 
will  consider  only  cholera  and  dysentery.  The  specific  nature  of  the 
former  disease  has  been  demonstrated  by  clinical  observation  and 
epidemiology,  as  well  as  by  Koch's  discovery.  The  author  must 
expand  at  some  length  upon  dysentery.  Most  clinicians  hold  it  to 
be  a  disease  perfectly  defined  and  possessing  full  autonomy.  Bacte- 
riological investigations,  however,  seem  to  lead  to  a  quite  different 
conclusion. 

Certain  authorities  attribute  dysentery  to  amebae.  Numerous 
observations  reported  by  Kartulis  seem  to  be  convincing.  Recent 
researches  of  Marchoux  demonstrate  that  amebse  may  produce  in 
cats  a  disease  analogous  to  dysentery  and  even  induce  hepatic 
abscesses.  This  experimental  result  confirms  those  observations  in 
which  protozoa  only,  in  the  absence  of  all  bacteria,  were  found  in 
the  pus  of  dysenteric  abscesses  of  the  liver. 

Numerous  observations  have  been  recorded  in  which  ameba3 
were  not  found.  On  the  other  hand,  bacteriologists  have  described 
various  bacteria  detected  in  cases  of  dysentery.  Some  have  noted 
special  microbes  of  the  bacillary  form  (Ziegler,  Babes,  Ogata),  or 
presenting  the  appearance  of  diplococci  (Silvestre) ;  others  have  met 
with  bacteria  which  were  already  known,  such  as  the  streptococcus, 
bacillus  pyocyaneus,  and  proteus  vulgaris.  The  majority  of  authori- 
ties, however,  have  isolated  bacilli  related  to  the  colon  bacillus  or 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORG  A  \is.m      .177 

•occupying  an  intermediate  position   between   the  latter  and   the 
typhoid  bacillus;  it  will  suffice  to  cite  the  namee  of  Kiel,-.  Chante- 
incssc,  Wiihil,  ( i  rigorierT,  Laveran,  Arnaud,  and  especially  Oelli  and 
Shiga,  who  have  recorded  highly  intere  ting  re  earchee  on  thi 
ject. 

Kxperiment.ing  with  dysenteric  dejecta  kindly  senl  him  by  con- 
freres practising  in  countries  where  the  disease  i  endemic,  the 
author  found  no  amebffl  in  any  instance,  bu1  a  bacillus  resembling 
the  ordinary  bacillus  coli.  It  readily  developed  in  bouillon,  to  which 
it  imparted  a  very  disagreeable  put  rid  odor.  Agar-agar  was  covered 
by  a  viscid,  thick  layer;  gelatin  was  aot  liquefied,  bul  small  gaseous 
bullae  weiv  at  limes  seen  iii  its  deeper  j > ; 1 1 •  i ~ :  mill,  was  generally 
coagulated  within  forty-eigh.1  hours,  and  the  medium  became  acid. 
On  potatoes  a  yellowish  culture  was  obtained. 

What  right  have  we  to  conclude  thai  this  bacillus  is  the  cause  of 
the  disease?  Have  we  not  in  the  presence  of  the  ordinary  colon 
bacillus,  a  constant  resident  of  the  human  intestine?  The  question 
is  certainly  difficult  of  solution.  In  favor  of  the  pathogenic  role  of 
this  bacterium  its  action  upon  animals  may  be  advanced,  which 
action  varies  according  to  the  degree  of  gravity  of  symptoms  observed 
in  man.  Another  argument  in  support  of  the  pathogenic  role  of  this 
microbe  is  based  upon  the  fact  that  it  produces  extremely  powerful 
toxins  in  culture  media,  The  sterilized  cultures  when  injected  into 
the  veins  of  rabbits  cause  diarrhea  which  at  times  is  so  severe  as 
to  be  almost  a  continuous  flow.  These  facts  suffice  to  establish  the 
individuality  of  the  dysenteric  colon  bacillus.  Another  fact  which 
imparts  to  it  a  particular  feature  and  conclusively  shows  its  patho- 
genic role  in  man  is  that  the  serum  of  patients  convalescent  from 
dysentery  agglutinates  the  dysenteric  colon  bacillus,  but  does  not 
agglutinate  the  ordinary  colon  bacillus.  This  was  noticed  by  the 
author  and  by  Celli  and  Shiga.  Flexner1  has  obtained  agglutination 
with  the  serum  of  patients  suffering  from  bacterial  dysentery,  while 
the  result  has  been  negative  in  the  case  of  amebic  dysentery.  The 
history  of  dysentery  is,  therefore,  to  be  divided  into  two. 

Choleriform  and  Dysenteriform  Ententes.  Alongside  of  the  spe- 
cific intestinal  infections  spoken  of  above  are  to  be  placed  common 
infections  which  simulate  them. 

Choleriform  gastroenteritis,  which  has  long  been  known,  resembles 

1  Flexner.  On  the  Etiology  of  Tropical  Dysentery.  Bulletin  of  the  Johns  Hopkins 
Hospital,  October.  1900. 


478 


IXFECTIO  US  DISK. I sj-s. 


genuine  cholera  by  its  symptoms.  Distinction  between  the  two  has 
been  based  upon  epidemiological  data.  Bacteriology  has  demon- 
strated the  absence  of  the  comma  bacillus  in  such  cases,  of  which 
numerous  examples  are  every  year  observed  during  the  hot  season, 
even  in  temperate  climates.  Likewise,  dysenteriform  ententes  are 
met  with  in  the  form  of  small  epidemics.  The  stools  contain  no 
amebse,  but  a  bacillus  distinctly  different  from  the  dysenteric  colon 
bacillus  above  described. 

The  fact  that  such  analogous  manifestations  are  produced  by 
different  parasites  is  not  to  be  wondered  at.  It  is  well  known  that 
certain  poisonings  are  expressed  by  symptoms  similar  to  those  of 
cholera;  such,  for  instance,  is  the  case  in  poisoning  by  tartar  emetic. 
On  the  other  hand,  intoxication  by  corrosive  sublimate  gives  rise 
to  lesions  and  symptoms  comparable  to  those  of  dysentery.  Clinical 
observation  is  not  yet  sufficient  to  give  us  an  accurate  idea  of  the 
nature  of  all  these  acute  ententes;  it  does  not  yet  enable  us  to 
trace  them  with  certainty  to  their  cause,  to  determine  the  infectious 
agents  responsible  for  their  development,  or  even  to  discern  with 
precision  infections  from  toxic  manifestations.  These  remarks  are 
equally  applicable  to  cholera  and  dysentery.  Hence  it  seems  to 
me  that  the  present  task  of  the  clinician  is  to  determine  and  describe 
the  differential  characters  which  will  lead  to  definite  distinction  of 
the  diverse  forms  of  dysentery  and  to  concordance  of  clinical  obser- 
vations with  bacteriological  findings. 

Choleriform  Gastroenteritis  and  Seasonal  Diarrheas.  Seasonal 
diarrheas  may  assume  either  choleriform  or  dysenteriform  characters. 

The  frequency  of  choleriform  diarrhea  varies  somewhat  from  one 
year  to  another,  as  may  be  seen  from  the  following  figures : 


>. 

s> 

£3 

b 

g 

e 

-« 

CO 

? 

Year. 

s 

e 

a. 

e 

<0 

I-* 

1 

1 

"S, 

O 

© 

to 

u 

c 
o 
Eh 

1896 

2 

2 

3 

4 

6 

1 

18 

1897 

1 

4 

10 

5 

20 

1898 

o 

2 

20 

24 

1 

l 

1 

52 

1899 

4 

.    . 

2 

1 

2 

1 

9 
6 

19 
10 

7 
5 

3 

l 

43 

1900 

27 

Total 

4 

2 

3 

3 

13 

31 

60 

37 

4 

l 

2 

160 

Seasonal  influence,  although  undoubted,  is  not  always  the  same.. 
Some  cases  are  at  times  met  with  during  the  cold  season.  The 
greatest  number,  however,  occur  in  August.     This  is  indicated  by 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.      479 

my  statistics,  but  Full)'  shown  by  those  of  the  French  army,    h  may 
be  seen  therein,  for  example,  tfyal  the  monthly  morbidity  of  diarrhea 
amounts  to  750  cases  in  June,  L350  in  July,  reaches  L700  in  Au| 
and  falls  to  looo  or  I  LOO  during  the  following  month. 

The  influence  of  heat,  ingestion  of  fruits  and  ice  water  do  Dot 
suffice  id  explain  ihe  genesis  of  the  phenomena.  'I  li'-  rdle  of  water 
must  first  be  taken  into  account.  The  qoxou  influence  of  the 
latter  was  recognized  byancienl  observers,  particularly  by  Hippoc- 
rates, and  has  been  demonstrated  by  numerous  contributions  of 
recent  period.  It  has  thus  been  learned  thai  epidemics  of  diarrhea 
sometimes  coincide  wifli  (hose  of  catarrhal  icterus,  typhoid,  and 
malarial  fevers.  In  Paris  diarrhea  and  typhoid  regularly  appear 
when,  in  summer,  Seine  water  is  drunk  instead  of  spring  water.  It 
should  not  be  concluded,  however,  that  alterations  in  water  suffice 
of  themselves  to  account  for  the  frequency  of  seasonal  diarrhea. 
Heat  seems  to  disturb  the  functions  of  the  intestine  and  hinder  the 
secretion  of  ferments;  it  leads  to  drinking  of  considerable  quantities 
of  liquids  which  dilute  and  weaken  the  digestive  juices.  Moreover, 
aliments  are  more  readily  altered  and  fermented  in  the  hot  season. 
Lastly,  a  part  is  played  by  overexertion,  as  is  so  frequent  ly  observed 
among  soldiers  during  fall  maneuvers  and  in  the  time  of  war. 

Unlike  genuine  cholera,  diarrheas,  even  when  assuming  choleri- 
form  appearance,  do  not  seem  to  be  due  to  a  specific  agent.  The 
opinion  is  gaining  ground  that  the  colon  bacillus  is  the  principal 
agent  concerned.  This  microbe  acts  by  secreting  toxic  substances 
in  the  alimentary  canal,  and  thus  gives  rise  to  the  development  of 
morbid  manifestations.  The  principal  poison  contained  in  the  stools 
was  found  by  Dr.  Robert,  who  pursued  researches  in  our  laboratory, 
to  be  a  substance  which  is  precipitated  by  alcohol.  Its  injection 
into  the  rabbit  causes  diarrhea,  hypothermia,  myosis,  and  at  times 
nystagmus  and  convulsions.  If  the  animal  recovers,  hypothermia 
is  followed  by  hyperthermia,  which  may  be  considered  as  a  reaction 
of  the  organism.  These  results,  when  compared  with  those  obtained 
by  the  employment  of  sterilized  cultures  of  the  colon  bacillus,  lead 
us  to  the  conviction  that  the  symptoms  of  gastroenteritis  may 
readily  be  explained  by  the  theory  of  intoxication.  Some  author- 
ities hold  dehydration  responsible  for  cramps.  This  interpretation 
is  not  plausible,  since  the  intensity  of  cramps  is  related  to  the 
gravity  of  the  phenomena  rather  than  to  the  amount  of  a  1  vine 
evacuations.     Moreover,  cramps  may  appear  with  the  first  stools. 


480  INFECTIO  US  DISEASES. 

and  may  at  times  precede  them.  'When  the  general  condition  is 
improved,  cramps  disappear,  while  diarrhea  still  continues. 

The  toxins  are  rejected  by  means  of  vomiting  and  diarrhea,  which 
represent  reactionary  phenomena  designed  for  the  elimination  of 
the  poisons.  Hence,  administration  of  a  purgative  and  lavage  of 
the  stomach  often  relieve  the  disturbances  by  completing  nature's 
task. 

Among  the  organs  affected  the  liver  must  first  be  mentioned. 
In  one-eighth  of  the  cases  this  gland  is  enlarged  and  often  painful 
on  palpation.  The  liver  must  struggle  against  the  toxins  and 
protect  the  organism;  but  it  is  often  injured  in  its  resistance,  for 
this  organ  is  constantly  found  degenerated  at  the  necropsj'.  The 
kidneys  are  seldom  involved,  albuminuria  is  quite  rare,  which  I 
have  observed  only  in  one-seventh  of  the  cases. 

The  mortality  from  seasonal  gastroenteritis  is  not  very  high. 
Out  of  a  total  of  160  patients  we  lost  14  (8.7  per  cent.).  In  most 
cases  death  occurs  at  the  end  of  three  or  four  days.  In  certain 
instances,  however,  it  supervenes  speedily.  Thus,  a  young  man, 
twenty-three  years  of  age,  was  taken  sick  on  August  26,  1899,  at 
6  a.m.,  with  fetid  diarrhea  and  vomiting.  He  was  brought  to  the 
hospital  on  the  same  clay  at  4  p.m.  The  face  was  cyanosed,  the 
extremities  cold  and  blue,  the  pulse  thready,  the  patient  unconscious 
with  a  central  temperature  at  105.1°  F.  (40.6°  C).  In  spite  of 
injections  of  caffein  and  of  artificial  serum  he  succumbed  an  hour 
later,  less  than  twelve  hours  after  the  onset  of  the  attack.  At  the 
necropsy  intense  congestion  of  the  intestines,  prominence  of  Peyer's 
patches,  and  dilatation  of  the  right  heart  were  the  only  alterations 
discovered. 

Dysenteriform  Enteritis.  Dysenteriform  enteritis  is  observed, 
especially  in  children,  and  is  not  as  frequent  as  choleriform  enteritis. 
Their  isolation  is  not  thought  to  be  as  necessary  as  that  of  persons 
suffering  from  the  choleriform  disease;  we,  therefore,  observed  only 
seven  cases  in  1899  and  two  in  1900. 

The  author  undertook  some  bacteriological  investigations  upon  his 
patients.1  Information  furnished  by  direct  examination  is  generally  of 
little  importance.  In  no  instance  have  I  found  amebse.  On  the 
other  hand,  the  microscope  revealed  a  more  or  less  marked  number 
of  microbes,  some  of  which  were  round,  others  in  the  form  of  rods. 

1  Roger.  Recherches  bacteriologiques  sur  l'ent6rite  dysent£riforme.  Presse  meYlicale, 
January  3,  1900. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       l-l 

In  slight  cases  the  tnicrobic  forms  were  quite  numerous.    In  \ 
cases  one  type  predominated,  viz.,  a  quite  large  rod,  resembling  by 
its  form  and  size  the  bacillus  of  anthrax,  bu1  differing  from  it  \>y 
its  rounded  extremities.     H  measured  5/<  to  6/<  in  length  and  I  '■'•." 
or  1.5//  m  breadth.    The  cultures   prepared  with   the  mucu 
the  dysenteriform  discharges  likewise  revealed  uumeroui  microbic 
varieties  in  slight  cuscs  and  predominance  of  certain  bacilli  in  g 
ones. 

In  the  presence  of  these  mierobie,  wiriHie-   no  definite  conclusion 
could  be  drawn.     I  therefore  resorted  to  the  method  of  inoculation 

Fig.  36, 


Bouillon  culture  of  bacilli  found  in  dysenteriform  enteritis  (five  hours  old). 

of  the  cultures  into  animals.  After  a  sojourn  of  twenty-four  hours 
in  the  incubator  the  bouillon  sown  with  intestinal  mucus  was 
injected,  into  rabbits  by  the  intravenous  route  in  the  dose  of  half  a 
cubic  centimeter.  All  the  animals  succumbed,  most  of  them  in  less 
than  twenty-four  hours.  "When  a  small  drop  of  blood  was  examined 
under  the  microscope  a  variable  number  of  bacilli  were  seen  which 
were  at  times  slightly  encapsulated.  It  would  seem  as  if  the  animal 
had  died  of  anthrax.  In  fact,  the  bacilli  are  quite  large.  They 
measure  in  the  blood  from  5«  to  6«  in  length  and  1.3 «  to  1.5 ft 
in  breadth.  These  microbes,  however,  can  readily  be  distinguished 
from  the   bacillus    anthracis   by   the    following  characters:     They 

31 


482 


INFECTIOUS  DISEASES. 


are  not  as  long,  and  are  at  times  so  short  as  to  be  liable  to  be 
mistaken  for  micrococci;  they  are  decolorized  by  Gram's  method 
and  rounded  at  their  extremities ;  finally,  some  present  a  constriction 
at  their  middle  part ;  in  the  latter  instance  the  extremities  are  oval, 
hence  the  appearance  is  that  of  a  diplococcus.  When  the  bacillus 
divides  at  the  constricted  point  each  part  simulates  a  micrococcus; 
but  these  newly  formed  elements  soon  become  elongated  and  assume 
the  characteristic  form. 

Cultures  succeed  in  all  of  the  usual  nutrient  media.     For  instance, 
a  bouillon  culture  becomes  turbid  at  the  end  of  four  or  five  hours. 


Fig.  37. 


Same  culture  (forty-eight  hours  old). 

If  it  is  examined  at  that  time  (Fig.  36)  numerous  rods  measuring 
4//  to  6//  in  length  and  1//  in  breadth  are  found;  others  are  in  pairs 
measuring  3//  to  3.5//  by  l/£.  On  the  following  days  (Fig.  37)  the 
microbes  are  more  slender  and  measure  mostly  2//  or  3//  by  0.8/a 
Culture  on  vegetables  has  a  different  appearance.  (Fig.  38.) 
The  bacilli  are  more  slender  and  generally  shorter  and  mixed  with 
oval  elements,  often  agglutinated  by  a  viscid  substance  which  renders 
staining  very  difficult.  The  elements  measure  0.75//  to  1//  in  length, 
1.25//  to  0.5//  in  breadth. 

This  bacillus  is  motile,  stains  readily,  but  is  decolorized  by  Gram's 
method.     The  results  obtained  upon  animals  show  that  it  possesses 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM,       !-.; 

a  marked  predilection  for  the  large  intestine;  even  when  injected 
through  the  veins  it  localizes  itself  in  the  terminal  pari  of  the 
digestive;  true.!,. 

The  liver  exercise:-;  a  destructive  action  upon  this  bacillus  when 
the  culture  is  very  young  i.  <■.,  while  il  contain  very  little,  if  any, 
toxin.  Animals  inueiilaieil  under  these  conditions  through  the 
portal  vein  readily  withstand  doses  which  are  fatal  when  injected 
by  the  peripheral  veins,  in  mosl  instances  destruction  of  the 
bacilli  is  complete.  In  two  cases,  however,  their  \,\(~<-wc<-  induced 
hepatic  abscesses.    The  pyogenic  properties  a1  times  manifested  by 


Kir;.  38. 


Culture  on  carrot  (twenty-four  hours  old). 

this  microbe  explain  this  result:  it  is  to  be  noted,  however,  that 
this  is  not  an  event  of  common  occurrence.  Having  injected  various 
pyogenic  microbes,  such  as  the  staphylococcus  aureus,  strepto- 
coccus, and  colon  bacillus,  into  thirty-three  rabbits  by  the  portal 
vein,  I  have  in  no  case  obtained  similar  results. 

In  view  of  the  constant  presence  of  the  microbe  in  the  cas  a 
examined  by  me  and  the  effects  produced  upon  animals.  I  am  in- 
clined to  consider  it  as  the  cause  of  dysenteriform  enteritis.  This 
opinion  is  further  supported  by  the  fact  that  I  have  not  been  able 
to  find  the  same  agent  in  the  stools  of  healthy  individuals  or  of 
patients  suffering  from  choleriform  enteritis. 


484 


IXFECTIO  US  DISEASES. 


It  may,  therefore,  be  asked  whether  my  microbe  represents  a  new 
species.  In  examining  the  numerous  works  published  on  dysentery 
I  have  found  but  two  bacteria  which  may  be  compared  with  mine. 
One  of  them  is  described  by  Ogata;  the  other,  which  has  several 
times  been  encountered  in  dysentery,  is  identified  with  proteus 
vulgaris. 

Ogata's  bacillus1  is  pathogenic  for  the  mouse,  the  guinea-pig,  and 
the  cat;  like  mine,  it  liquefies  gelatin.  It  differs  clearly,  however, 
in  that  it  stains  by  Gram's  method.     Its  morphology  is  not  identical ; 


Proteus  vulgaris.     Culture  upon  carrot  (twenty-four  hours  old). 

the  author  describes  it  as  a  slender  rod  comparable  to  the  tubercle 
bacillus. 

As  regards  the  proteus  vulgaris,  it  has  frequently  been  met  with 
in  patients  suffering  from  gastroenteritis  or  even  dysentery.  The 
morphological  and  biological  characters  are  not  identical;  there  are, 
nevertheless,  some  obvious  analogies — liquefaction  of  gelatin,  fetid 
odor,  same  action  upon  milk,  glucose,  saccharose,  etc.  The  dif- 
ferences are,  however,  sufficiently  clear  to  prevent  confusion. 
Proteus  vulgaris  hardly  develops  upon  slices  of  artichoke,  the  color 
of  which  it  does  not  modify.     Our  microbe  forms  upon  this  medium 


1  Ogata.     Zur  Aetiologie  der  Dysenteric     Centralblatt  f.  Bakt.,  1892,  Bd.  xi.,  S.  246. 


INFLUENCE  OF  INFECTIONS  UPON  TEE  ORGANISM.       i-., 

a  yellow  mass,  while  the  remainder  of  the  medium  assume*  a  col(  r 
of  intense  green.  The  surface  of  the  nutrient  medium  rapidly 
becomes  green  when  agar-agar  prepared  with  artichoke  water  i 
employed.  The  proteus  vulgaris  doe  not  develop  in  the  latter 
medium.  The  culture  of  my  microbe  upon  carrots  is  while,  quite 
thick;  that  of  the  proteus  vulgaris  is  scanty,  consisting  of  very  long 
filaments  and  rods,  intensely  stained.  I  Fig.  39.)  When  this  appear- 
ance is  compared  with  thai  furnished  by  my  bacillus  (Fig.  38),  the 
non-identity  of  (he  I. wo  bacilli  becomes  manifest  beyond  all  doubt. 

Serum  reaction  furnishes  another  distinctive  character.  I  em- 
ployed the  scrum  derived  from  animals  which  had  received  a  virulenl 
culture  of  my  bacillus  by  a  branch  of  the  portal  vein  and  which  had 
resisted  this  inoculation.  By  putting  one  drop  of  this  serum  in 
ninety-nine  drops  of  a  culture  twenty-four  hours  old,  agglutination 
of  the  bacillus  is  obtained  in  a  few  minutes.  The  proteus  is  not 
agglutinated,  even  when  a  tenfold  amounl  of  the  serum  is  employed. 

My  microbe  has  been  encountered  by  Dr.  Lemoine  under  similar 
conditions,  viz.,  in  the  course  of  an  epidemic  among  soldiers  house. 1 
in  the  ficole  Militaire.  He  isolated  the  bacillus  in  thirteen  a 
and  found  it  to  be  pathogenic  for  animals.  Finally,  I  h.  Barl  >ier  told 
me  he  had  found,  with  the  assistance  of  Dr.  Tollemer,  a  bacillus 
analogous  to  mine  in  an  epidemic  which  appeared  in  the  Hopital 
des  Enfants  Malades.  These  authors  practiced  inoculations  upon 
rabbits  and  found  intestinal  ulcerations  in  a  certain  number  of  them. 
In  one  case,  in  which  they  inoculated  the  virus  into  veins  of  the  ear, 
they  discovered  small  abscesses  in  the  liver  containing  the  same 
bacillus. 

Influence  of  Infectious  Diseases  upon  the  Liver. 

Microbes  may  reach  the  liver  by  various  routes.  They  sometimes 
spread  through  contiguity:  they  thus  invade  the  gland  as  a  result 
of  perihepatitis  or  even  pleurisy.  More  frequently  they  follow  one 
of  the  circulatory  systems  ramifying  in  the  organ:  the  portal  vein, 
the  hepatic  artery,  and  the  lymphatic  and  biliary  vessels.  In  almost 
all  infections,  but  more  particularly  in  those  which  tend  to  directly 
involve  the  intestines,  such  as  typhoid  fever,  the  liver  is  usually 
altered.  In  dysentery  the  amebic  find  their  way  into  its  depths 
in  company  with  other  parasites  which  cooperate  powerfully  to 
induce  suppuration.  The  hepatic  artery  is.  in  this  connection,  of 
less  importance:  it  is  through  it.  however,  that  septic  emboli  reach 


486  INFECTIOUS  DISEASES. 

the  liver,  especially  in  cases  of  ulcerative  endocarditis.  The  possi- 
bility of  hepatic  infection  through  the  lymphatic  vessels  has  not 
yel  been  well  investigated.  Hayem  and  some  other  authorities 
think  syphilitic  sclerosis  of  the  liver  is  induced  through  the  lymphatic 
channels.  Microbes  may  likewise  pass  from  the  intestine  to  the 
liver  by  way  of  the  biliary  channels;  thus  are  produced  angio- 
cholites  and,  consecutively,  biliary  lithiasis. 

The  liver  is  very  often  affected  in  the  fetus.  During  intra-uterine 
life  the  individual  is  in  relation  with  the  external  world  by  the 
umbilical  vessels,  and  it  is  through  them  only  that  pathogenic  germs 
can  invade  its  organism;  the  microbes  must,  therefore,  pass  first  to 
the  hepatic  gland,  which  may  sometimes  arrest  them  and  be  sub- 
jected to  their  action.  In  case  infection  becomes  generalized  the 
liver  is  the  organ  most  profoundly  affected,  as  is  notably  the  case 
in  syphilis  and  tuberculosis.  What  has  been  stated  concerning 
figurate  elements  is  equally  true  as  regards  toxins,  which  are  also 
capable  of  producing  disturbances  and  more  or  less  pronounced 
lesions  in  the  liver.  Moreover,  this  gland  must  neutralize  autogenic 
toxins  produced  in  excess  by  diseased  tissues  and  incompletely  elim- 
inated by  the  injured  kidneys. 

General  Characters  of  the  Infected  Liver.  In  spite  of  its  func- 
tional disturbances,  the  liver  may  appear  sound  under  macroscopic 
and  even  microscopic  examination.  More  frequently,  however,  it 
presents  various  alterations.  These  may  be  divided  into  two  groups : 
some  are  specific,  such,  for  instance,  as  syphilomata,  tubercles,  and 
nodules  of  glanders.  Others  are  ordinary  lesions,  and  may  be  encoun- 
tered in  the  majority  of  infections.  They  are  characterized  by  con- 
gestion, degenerations,  cellular  proliferations,  ending  at  times  in  the 
formation  of  small  nodules.  The  macroscopic  appearances  of  the 
liver  generally  depend  upon  congestion  and  cellular  degenerations. 

The  infectious  liver  is,  as  a  rule,  enlarged  and  soft,  the  latter 
character  being  the  more  pronounced  the  more  rapid  the  evolution 
of  the  disease.  Its  color  varies  according  as  congestion  or  degenera- 
tion dominates.  In  the  former  instance  the  liver  is  red;  such  is  the 
case  in  typhoid  fever,  in  the  first  days  of  eruptive  fevers,  in  cholera, 
and  acute  intermittent  fevers.  When  degeneration  is  predominant 
the  liver  is  pale,  yellowish,  anemic,  at  times  covered  with  ecchy- 
moses,  which  may  be  more  or  less  extensive. 

When  the  infectious  liver  is  examined  at  an  advanced  period,  two 
orders  of  cellular  lesions  are  found:  degenerations  of  the  hepatic  cells 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       i-7 

and  accumulation  of  round  cells.    The  celli    well,  compre     the  cap- 
illaries, and  obliterate  their  lumina  ;  the  initial  congestion  i   folio 
hy  anemia.    The  cells  are  swollen  and,  al  leasl  in  the  beginning, 
contain  several  nuclei  and  presenl  fine  karyokinetic  figure  .     I 
subsequently  undergo  hyaline  and  vitreoui  degeneration,  ac  i    ob-' 
served  particularly  in  typhoid  fever  and  cholera,    [n  rarer  instance 
the  process  is  characterized  by  coagulation  necro  i  .  by  transforma- 
tion of  the  cells  into  a  vitreous  mass  withoul  any  colorable  nucleus, 
This  process  is  localized  and  of  less  importance;  it  u  the  death  of 
the  cells.    Reactionary  phenomena  are  coincidently  produced  which 
account  for  proliferation  of  the  nuclei.     Fatty  degeneration  is  very 
rare;  it  occurs  only  in  diseases  of  long  duration,  in  chronic  suppura- 
tions, in  which  it  is  explained  by  diarrhea    and  cachexia  of  the 
patients.    The  biliary  channels  at  the  same  time  undergo  prolifera- 
tion and  newly-formed  canaliculi  appear,  which  are  especially  ma 
in  subacute  forms. 

The  interstitial  lesions  consist  in  the  formation  of  infectious 
nodules  (Friedreich,  Wagner,  Weigert,  Hanot,  Legry).  These  are 
rounded,  oval,  or  triangular  in  shape,  and  occupy  any  point  of  the 
lobule,  filling  about  one-twentieth  part  of  it.  They  are  formed  of 
masses  of  round  cells  contained  in  a  granular  substance;  around 
them  the  hepatic  cells  have  suffered  granulofatty  degeneration.  The 
cells  constituting  them  are  probably  of  various  origin;  leucocytes, 
cells  of  the  interstitial  tissue,  probably  also  altered  hepatic  cells  con- 
tribute to  form  the  masses.  Finally,  instead  of  being  united  in  the 
form  of  nodules,  the  cells  may  be  distributed  so  as  to  form  inter- 
lobular or  intralobular  bands — a  true  embryonal  cirrhosis  which  may 
subsequently  develop  into  chronic  sclerosis — well  studied  by  Hanot 
and  his  disciple,  Gaston. 

Semiology  of  Infectious  Liver.  There  is  no  method  enabling  the 
physician  to  determine  during  life  the  functional  value  of  the  liver. 
To  this  end  rather  crude  procedures  and  indirect  means  are  employed. 
For  instance,  the  size  of  the  organ  is  taken  as  a  basis.  It  is  not 
possible,  however,  to  establish  a  relationship  between  atrophy  or 
hypertrophy  of  the  liver  and  its  function.  It  is  better  at  times  to 
judge  the  state  of  this  organ  by  disturbances  observed  in  other  parts 
of  the  economy.  These  disturbances  are  of  two  orders.  Some, 
probably  of  reflex  origin,  are  expressed  by  pulmonary  congestion 
localized  at  the  right  base  and  a  bruit  de  galop  of  the  right  heart. 
The  others,  more  important,  are  of  toxic  origin.    Delirious  or  coma- 


488  INFECTIO  US  DISEASES. 

tose,  even  convulsive,  manifestations  may  occur.  The  functions  of 
the  kidneys,  however,  are  more  disturbed  than  the  nervous  system. 
Hepatic  inadequacy  results  in  renal  inadequacy,  as  expressed  by 
decreased  secretion.  At  the  same  time,  in  consequence  of  disorders 
induced  by  the  hepatic  disturbances  in  organic  metabolism,  urea  is 
diminished,  the  extractive  matters  are  increased,  and  abnormal  sub- 
stances, such  as  albumin,  peptones,  etc.,  appear,  and  what  is  more 
peculiar  to  hepatic  disorders,  various  pigments,  normal  or  modified 
biliary  pigments,  and  urobilin  are  present  in  the  urine. 

Icterus  is  quite  rare  in  the  course  of  infections  and,  when  present, 
is  of  rather  unfavorable  prognostic  significance.  In  a  large  number 
of  cases,  however,  it  is  of  a  simple  catarrhal  nature,  and  does  not 
render  prognosis  any  more  serious.  Some  authors  believe  this  catar- 
rhal icterus  is  due  to  the  fact  that  the  bile  is  more  viscid  and  is 
partially  retained;  others  assert  that  there  is  polycholia. 

In  certain  instances  the  symptoms  assume  the  type  of  those  ob- 
served in  the  course  of  grave  icterus.  This  has  occurred  in  cholera, 
scarlatina,  and  typhoid  fever;  the  cellular  alterations  are  so  intense 
that  autointoxication  by  hepatic  inadequacy  is  produced. 

Action  of  Infections  upon  the  Pancreas. 

The  difficulty  of  recognizing  disorders  and  lesions  of  the  pancreas 
during  life  and  its  rapid  putrefaction  after  death  have  greatly  hin- 
dered its  study.  In  spite  of  important  works,  among  others  those 
of  Carnot1  and  Klippel,  we  are  in  possession  of  no  sure  symptoms 
enabling  us  to  determine  the  part  taken  by  the  pancreas  in  infectious 
processes. 

The  pancreas  may  be  affected  in  the  course  of  general  infections, 
such  as  measles,  variola,  pneumonia,  septicemias,  and  pyemias. 
Pancreatitis  may  also  occur  in  ententes,  typhoid  fever,  dysentery, 
and  cholera.  The  anatomico-pathological  study,  completed  by  ex- 
perimental investigations,  has  revealed  a  whole  series  of  lesions  from 
diffuse  to  hemorrhagic  and  suppurative  pancreatitis.  These  lesions 
may  be  repaired.  In  many  instances,  however,  as  in  the  case  of  the 
liver,  they  become  the  starting  point  of  scleroses,  and  may  subse- 
quently end  in  cirrhotic  atrophy  of  the  gland.  Pancreatic  diabetes 
is  probably  thus  engendered. 

1  Carnot.  Recherches  experimentales  et  cliniques  sur  les  pancreatites.  These  de 
Paris,  1898.  Richardiere  and  Carnot.  Maladies  du  pancreas.  Traits  de  m6decine  et 
de  therapeutique,  Paris,  1898,  t.  v.,  p.  9. 


INFLUENCE  OF  INFECTIONS  UPON  THE  ORGANISM.       |.-:. 

It  is  well  to  remark  that  sclero  i  may  occur  in  the  absence  of  .''II 
infection  of  the  gland  under  the  influence  of  toxin  engendered  in 
other  parts  of  the  organism.  Dr.  Carnol  ha  de  cribed  .'i  tubercular 
sclerosis  of  the  pancreas  w  hicli  may  be  compared  with  similar  scle- 
roses developing  in  oilier  organs  and  Qotably  thyroidian  sclero 

Influence  of  Infections  upon  the  Kidneys. 

The  study  of  renal  lesions  in  the  course  of  infectious  di 
comparatively  easy,  since  examination  of  the  urine,  especially  search 
for  albumin  and  casts,  enables  us  to  appreciate  the  functional  con- 
ditions and  lesions  of  the  kidneys. 

All  infections,  even  when  benign  and  localized,  may  give  rise  to 
renal  alterations.  Pneumonia  and  the  various  pneumococcic  infec- 
tions produce  diffuse  nephritis  remarkable  for  the  frequency  of 
hematuria.  Cholera  induces  renal  lesions  which  seem  to  play  an 
important  r61e  in  the  pathological  physiology  of  this  malady,  and 
explain  certain  symptoms.  Syphilis  and  tuberculosis  give  rise  to 
acute  or  chronic  processes. 

Among  infectious  diseases  scarlatina  causes  the  most  interesting 
renal  phenomena.  Albuminuria  is  frequent,  appearing  at  times  dur- 
ing the  stationary  period,  and  in  other  cases  during  convalescence. 
It  was  absent  in  only  one  of  the  author's  cases  ending  fatally — such 
fatal  cases  constituting  53  out  of  a  total  of  2157  scarlatina  cases. 
Scarlatinal  nephritis  is  generally  considered  to  be  of  little  gravity. 
It  is  true  that  even  when  it  gives  rise  to  uremic  phenomena,  recovery 
is  possible.  Besides  the  53  cases  above  mentioned,  the  author's 
statistics  show  663  other  patients  in  whom  scarlatina  was  compli- 
cated by  albuminuria,  and  who  recovered.  It  is  important  to  note, 
however,  that  although  the  acute  symptoms  subside  far  more  readily 
in  scarlatinal  nephritis  than  in  all  other  varieties,  the  patient  incom- 
pletely recovers.  Nephritis  too  often  passes  into  a  chrome  state 
either  because  albuminuria  persists  or  because  it  reappears  on  the 
slightest  occasional  cause. 

The  researches  of  Ponfick,  Langerhans,  Wissokovitch,  Biedl,  and 
Kraus  have  demonstrated  that  microbes  introduced  into  the  blood 
are  rapidly  eliminated  by  the  urine.  In  certain  instances  the  excre- 
tion of  bacteria  begins  at  the  end  of  fifteen  or  twenty  minutes. 
Their  passage  is  often  effected  without  any  injury  to  the  kidneys. 
It  is  intelligible,  however,  that,  according  to  the  degree  of  virulence 
of  the  germs  and  the  vulnerability  of  the  organ,  colonization  may 


490  IXFECTIO  US  DISEASES. 

occur,  the  microbes  being  there  arrested  and  producing  poisons 
which  prove  the  starting-point  of  nephritis.  In  other  instances  the 
toxins  are  brought  to  the  renal  glands  from  other  points  of  the 
economy.  The  role  of  the  kidne}^  in  the  elimination  of  poisons 
accounts  for  the  frequency  of  lesions  which  these  organs  suffer  in 
the  course  of  infectious  diseases. 

Influence  of  Infections  upon  the  Genital  Organs. 

Orchitis  complicating  mumps  is  never  observed  in  children;  it 
occurs  only  in  adults,  following  localization  in  the  parotid  glands,  and 
at  times  replacing  it  as  a  sort  of  metastasis.  In  rare  cases  orchitis 
develops  coincidently  with  parotiditis,  and  in  exceptional  instances 
it  represents  the  -first  and  even  the  only  manifestation  of  the  disease. 
The  testicular  inflammation  lasts  four  or  five  days,  and  never  ends 
in  suppuration.  Were  it  not  for  the  danger  of  tardy  atrophy  of  the 
testicle,  the  involvement  would  be  of  no  gravity  whatever.  When 
both  testicles  are  involved  prognosis  must  be  reserved  from  a  pro- 
creative  standpoint. 

Typhoid  fever  has  been  cited  among  infections  particularly  liable 
to  affect  the  testicles.  According  to  Chantemesse,  orchitis  occurs  in 
the  proportion  of  1  to  196  cases;  it  subsides  in  ten  or  twelve  days 
without  causing  atrophy  of  the  gland.  In  some  cases,  however, 
owing  to  localization  of  the  typhoid  bacillus,  suppuration  remarkable 
for  its  long  duration  has  occurred. 

The  ovaries  are  less  frequently  involved  than  the  testicles;  their 
participation  has,  however,  been  noted  in  typhoid  fever,  variola,  and 
mumps.  Like  other  parts  of  the  organism,  the  uterus  may  be 
affected  in  measles,  variola,  and  typhoid  fever. 

Influence  of  Infections  upon  Menstruation.  The  relations  between 
menstruation  and  the  development  of  erysipelas  have  long  been 
noted.  We  must  leave  aside  those  instances  in  which  the  coincidence 
is  accidental.  For  instance,  one  of  our  patients  had  already  had 
six  attacks  of  erysipelas;  the  seventh  attack  occurred  with  menstrua- 
tion. Genuine  menstrual  erysipelas  always  occurs  on  the  occasion 
of  menstruation.  These  erysipelas  attacks  are  generally  so  benign 
as  to  cause  no  anxiety,  and,  therefore,  few  patients  resort  to  the 
hospitals.  We  have  observed  but  16  such  cases  out  of  a  total  of 
1198  erysipelatous  women.  One  of  them  had  had  forty-six  attacks, 
always  coincident  with  menstruation. 


INFLUENCE  OF  INFECTIONS   iros   THE  ORGANISM       \w\ 

Erysipelas  may  al  times  replace  the  men  trual  flow.  A  woman 
twenty-one  years  of  age  had  had  her  firi  I  eryi  Ipelai  eleven  months 
before;  since  that  time  Bhe  had  six  more  attacks,  and  each  time  the 
cutaneous  inflammation  appeared  the  catamenial  discharge  failed  to 
occur.  She  entered  the  hospital  on  March  17th  for  a  quite  in 
erysipelas  replacing  menstruation.  On  April  Llth,  while  she  was 
still  in  our  wards,  the  incuses  appeared  in  a  regular  manner,  and 
erysipelas  did  riot  recur. 

In  three  oilier  cases  erysipelas  recurred  regularly  every  month 
before  puberty,  and,  at  this  period  the  cutaneous  manifestation* 
ceased  or  persisted.  A  woman,  forty-five  years  of  age,  told  the 
author  that  from  the  age  of  seven  years  to  thai  of  eighteen  she  had 
every  month  developed  a  slight  erysipelas;  at  the  age  of  eighteen 
menstruation  was  established  and  the  periodical  erysipelatous  attacks 
ceased.  She  had  one  attack  of  erysipelas  at  the  age  of  thirty-two 
years,  occurring  independently  of  the  menses.  The  menopause 
occurred  at  the  age  of  thirty-eight  years,  and  from  that  time  on. 
while  she  has  had  no  menstruation,  she  experienced  two  attacks  of 
erysipelas,  once  when  forty-one  years  old,  and  another  for  which  she 
resorted  to  our  wards,  at  the  age  of  forty-five  years. 

Of  all  infectious  diseases  variola  is  undoubtedly  the  one  which 
most  frequently  causes  menstrual  disturbances.  Uterine  hemor- 
rhages are  observed  in  11  or  12  per  cent,  of  the  cases  which  recover. 
Metrorrhagia  generally  occurs  at  the  period  of  invasion;  in  some  caa  a 
during  convalescence.  The  action  exercised  by  variola  upon  the 
uterus  is  so  marked  as  to  cause  bloody  discharges  even  after  the 
woman  has  reached  the  menopause.  This  occurred  in  a  patient 
forty-five  years  of  age,  in  whom  the  menopause  had  been  established 
six  months  before.  The  same  happened  in  a  twelve-year-old  child 
who  had  not  yet  begun  to  menstruate.  The  author  has  observed 
the  same  even  in  a  child  five  months  old. 

Menstrual  disturbances  are  particularly  frequent  in  fatal  cases  of 
variola.  Metrorrhagia  complicates  28  per  cent,  of  confluent  variola: 
it  is  never  absent  in  hemorrhagic  variola. 

According  to  our  statistics,  measles  gives  rise  to  premature  men- 
struation in  5  per  cent,  of  the  cases  and  scarlatina  in  10  per  cent. 

Influence  of  Infections  upon  Pregnancy  and  Lactation.  It  seems 
to  the  author  that  the  gravity  of  infections  in  pregnant  women  has 
been  somewhat  exaggerated.  In  this  connection  erysipelas  has  been 
a  special  subject  of  study.     Clinicians  had  long  since  noted  the 


492  INFECTIO  US  DISEASES. 

remarkable  relationship  existing  between  erysipelas  and  puerperal 
fever.  Bacteriological  researches  have  shown  that  the  same  microbe 
is  concerned  in  both  instances,  and  thus  have  confirmed  the  data  of 
observation.  The  facts,  however,  which  the  author  has  collected  do 
not  justify  thefears  of  accoucheurs  regarding  erysipelatous  infections. 

The  author  will  first  consider  the  influence  of  erysipelas  upon  the 
course  of  pregnancy.  Ancient  authors  dwelt  much  upon  the  fre- 
quencjr  of  abortions:  Wardevell  saw  24  abortions  out  of  25  cases. 
Recent  statistics  are  far  better :  Duchein  gathered  41  cases,  and  notes 
but  14  abortions.  Dr.  Legendre  observed  4  abortions  in  a  total  of 
13  cases.  The  author  has  received  44  pregnant  women  into  his 
wards.  In  25  of  these,  although  several  suffered  from  grave  ery- 
sipelas, pregnancy  continued  its  course.  Nineteen,  twelve  of  whom 
had  reached  full  term,  were  confined  in  our  wards;  the  other  con- 
finements took  place  in  the  seventh  or  eighth  month. 

Erysipelas  of  the  mother  does  not  seem  to  be  dangerous  for  the 
child.  All  those  which  were  born  at  full  term  survived  and  developed 
well.     Only  one  of  them  contracted  the  disease. 

Suckling  by  Infected  Women.  Shall  an  infected  woman  be  allowed 
to  suckle?  This  question  is  to  be  answered  according  as  infection  is- 
protracted  or  transitory.  In  the  former  instance  suckling  must  be 
interdicted;  such  is  the  rule  as  regards  typhoid  fever.  In  the  case 
of  transitory  infections  suckling  may  be  permitted. 

In  view  of  the  evil  effects  of  artificial  feeding  among  the  poorer 
classes,  the  author  first  permitted  erysipelatous  women  to  suckle 
their  children.  No  harm  resulting,  he  followed  the  same  rule  in  other 
infections  treated  in  his  wards.  The  result  seemed  to  be  highly 
gratifying.  Out  of  a  total  of  over  100  children,  only  two  were  in- 
fected; one  of  them  contracted  measles,  the  other  erysipelas  from 
the  mother.  In  both  instances,  however,  the  evolution  was  remark- 
ably benign.  The  other  children  presented  no  disturbance.  It  is  to 
be  remembered  that  infection  diminishes  the  lacteal  secretion  and 
may  necessitate  mixed  feeding  for  a  few  days.  Only  in  very  grave 
cases  of  variola  is  the  secretion  so  profoundly  altered  as  to  render 
suckling  impossible. 

The  rules  are  well  defined  as  regards  syphilis.  It  is  important  that 
the  mother  should  suckle  her  child.  The  laws  of  Colles  and  Profeta 
show  that  there  is  not  the  slightest  inconvenience  in  this  practice. 
If  either  of  them,  the  mother  or  the  offspring,  is  alone  contaminated, 
the  disease  is  not  transmitted  to  the  other. 


INFLUENCE  OF  INFECTIONS  urns  TEE  ORGANISM.       !!».", 

As  regards  hilxTculosis,  the  rule  is  the  reverse  of  the  preceding. 
Suckling  must  be  forbidden.  Not  because  the  milk  i  <■  dan- 
gerous— Koch's  bacillus  very  seldom  passes  into  the  milk  bul  in 
the  course,  of  this  chronic  disease  the  milk  Is  of  an  inferior  quality 
and,  on  the  other  hand,  it  is  wise  to  diminish  the  chances  of  con- 
tagion by  limiting  the  contact  between  the  mother  and  her  child. 

To  sum  up,  while  suckling  is  to  be  forbidden  in  chronic  infections, 
except  syphilis,  or  in  prolonged  acute  infections,  il  may  I"-  permitted 
in  other  cases. 


CHAPTEE    XVII. 
EVOLUTION  OF  INFECTIOUS  DISEASES. 

Incubation.  Duration  of  Incubation  in  Principal  Infections.  Invasion.  Stationary 
Period.  Course  of  Local  and  of  General  Phenomena.  Clinical  Forms.  Clinical 
Forms  of  Pneumonia  and  of  Typhoid  Fever.  Termination  of  Infectious  Diseases. 
Defervescence.  Crises.  Urinary  and  Urotoxic  Crises.  Study  of  Urinary  Crises  in 
Pneumonia,  Erysipelas,  Scarlatina,  and  Catarrhal  Jaundice.  Convalescence.  Acci- 
dents of  Convalescence.  Relapses  and  Recurrences.  Passage  of  Acute  Infection 
into  a  Chronic  State.  Death.  Death  by  Mechanical  Cause.  Death  by  Intoxica- 
tion.    Death  by  Post-infectious  Cachexia. 

The  evolution  of  infectious  diseases  may  be  divided  into  four 
periods  or  stages:  incubation,  invasion,  stationary  period,  and  de- 
cline. 

Incubation  corresponds  to  the  time  elapsing  between  the  deposi- 
tion of  a  pathogenic  agent  in  the  organism  and  the  first  appearance 
of  morbid  manifestations.  Invasion,  which  indicates  the  beginning 
of  the  disease,  may  be  abrupt  or  insidious.  In  the  former  instance, 
the  moment  at  which  the  disease  sets  in  may  be  noted  in  a  precise 
manner.  Such  is  the  case,  for  instance,  when  an  apparently  healthy 
individual  is  suddenly  seized  with  a  violent  chill.  The  passage  from 
a  sound  into  a  morbid  state  occurs  without  transition,  and  is  sharply 
defined.  In  other  cases  the  symptoms  develop  gradually,  so  that  an 
intermediate  period  of  malaise  or  indisposition  elapses,  and  it  is  then 
very  difficult  to  determine  the  beginning  of  the  disease.  The  devel- 
oped disease  remains  for  a  certain  time  stationary,  presenting  more 
or  less  marked  oscillations  of  aggravation  and  amelioration;  this  is 
the  stationary  period.  Then  comes  the  decline  which,  like  invasion, 
may  be  sudden  or  progressive.  In  the  former  case,  a  sudden  defer- 
vescence or  crisis  is  said  to  occur,  and  the  expression  decline  is 
reserved  for  the  slow  course  toward  recovery. 

After  the  favorable  termination  of  the  disease  there  remains  a 
period,  at  times  of  considerable  length,  during  which  the  functions 
are  re-established  progressively,  and  gradually  become  normal.  This 
is  convalescence. 

Finally,  even  when  the  morbid  acts  seem  to  be  terminated,  the 
organism  may  not  have  completely  resumed  its  former  mode  of  life. 


EVOLUTION  OF  INFEOTI0U8  DI8EA8E8.  !!•., 

Certain  anatomical  changes  or  functional  disturbance*  may  pei 
remaining  inappreciable  even  on  profound  examination;  buf  s  Bilent, 
insidious,  morbid  evolution  continues  which  terminate*  a1  the  end  of 
several  years  in  symptoms,  disorders,  and  affection*  which  are  not 
readily  traced  to  their  origin. 

Such  are  the  various  periods  observable  in  the  course  of  infect 
discuses.    This  division  is  appreciable,  especially  when  evolution  fol- 
lows an  acute  course.     If    is  far  less  definite  in  ca  e    of  chronic 
infection. 

Moreover,  the  morbid  evolution   may  be  constantly  modified  by 

some  unexpected  event,  or  complication,  or  i1  may  be  interrupted 

by  death. 

Incubation. 

Incubation,  as  above  stated,  is  the  time  elapsing  between  the  depo- 
sition of  the  morbid  germ  in  the  tissue  and  the  appearance  of  the 
first  local  or  general  symptoms  of  the  disease.  This  definition,  which 
is  applicable  only  to  neuroinfections,  must  be  slightly  modified  when 
the  process  is  one  of  autoinfection.  In  the  latter  case  the  germ  is 
not  deposited  in  the  organism  from  without,  and  therefore  the  st. •!<:<' 
of  incubation  begins  at  the  moment  when  the  dormant  microbe, 
until  then  inoffensive,  becomes  pathogenic  under  the  influence  of 
some  excitation.  It  is  intelligible  that  if  the  determination  of  the 
period  of  incubation  is  a  matter  of  difficulty  in  the  former  case,  it 
is  almost  an  impossibility  in  the  latter. 

During  the  period  of  incubation  the  organism  does  not  always 
remain  passive;  it  may  endeavor  to  destroy  the  invading  microbes. 
Should  it  fail  to  do  this,  the  disease  becomes  manifest.  It  is  there- 
fore incorrect  to  say  that  an  infectious  disease  is  a  reaction  aroused 
by  the  introduction  of  a  microbic  agent,  since  morbid  reaction  does 
not  necessarily  occur  in  all  instances.  The  microbe  may  be  de- 
stroyed or  remain  quiescent  at  the  point  where  it  was  de]  ><  sited.  In 
order  that  morbid  manifestations  may  appear,  a  period  of  prepara- 
tion is  required  which  represents  a  first  defeat  of  the  organism.  ^  e 
are  thus  led  to  admit  the  occurrence  of  three  successive  stages  at  the 
beginning  of  all  infections :  introduction  or  exaltation  of  the  microbe, 
a  latent  period  of  development  corresponding  to  incubation,  and  a 
reaction  of  the  organism  corresponding  to  invasion,  that  is.  to  the 
beginning  of  the  disease. 

The  period  of  incubation  may  be  silent  and  unattended  by  morbid 
manifestations;  then,  at  a  given  moment,  a  reaction  is  produced, 


496  INFECTIOUS  DISEASES. 

often  quite  suddenly.  Such,  for  instance,  is  the  beginning  of  lobar 
pneumonia.  It  is  a  very  curious  fact  that  the  microbe  should  be 
able  to  continue  secreting  its  toxins  in  a  progressive  manner  without 
giving  rise  to  any  disturbance  on  the  part  of  the  organism,  and  that 
the  organism  should  act  so  tardily  when  it  is,  as  it  were,  saturated 
with  soluble  toxic  products. 

Even  when  the  beginning  is  sudden  it  is  often  difficult,  if  not 
impossible,  to  determine  the  period  of  incubation,  since  we  are  not 
always  able  to  decide  as  to  the  moment  when  contagion  occurred. 
Most  frequently  patients  are  unable  to  give  an}^  information.  In  the 
eruptive  fevers,  except  variola,  it  is  seldom  possible  to  determine 
under  what  conditions  contamination  has  taken  place.  Even  when 
patients  know  that  they  have  been  in  contact  with  an  infected  person 
they  do  not  remember  with  accuracy  the  day  on  which  they  saw  the 
diseased  individual.  Others  have  passed  several  days  at  the  bedside, 
and  it  is  evidently  impossible  to  know  at  what  moment  contamina- 
tion was  effected.  Finally,  in  cases  of  prolonged  incubation,  it  may 
always  be  asked  whether  a  later  contamination  which  has  remained 
unnoticed  has  not  taken  place.  Consequently,  in  order  to  reach 
unassailable  results,  a  series  of  circumstances  are  required  which  are 
seldom  realized.  The  perusal  of  works  on  incubation  leads  to  the 
conviction  that  an  average  duration,  varying  only  within  narrow 
limits,  exists  for  the  majority  of  diseases.  It  would  be  a  grave  error, 
however,  to  overlook  the  fact  that  the  period  of  incubation  is  at 
times  shortened  and  at  other  times  prolonged  within  considerable 
limits.  Nothing  in  this  regard  is  more  demonstrative  than  the  his- 
tory of  venereal  diseases,  for  it  is  in  this  class  of  affections  that  the 
moment  of  contamination  may  be  determined  most  exactly,  and  that 
interpretation  is  easiest.  With  syphilis,  for  example,  the  chancre 
generally  makes  its  appearance  from  twenty  to  thirty  days  after 
infecting  intercourse.  This  average,  which  is  sufficiently  wide  in  its 
scope,  does  not,  however,  include  those  cases  in  which  the  beginning 
is  manifest  at  the  end  of  ten  days,  nor  those  in  which  it  is  delayed 
until  the  fortieth  or  even  fiftieth  day.  The  variability  of  this  period 
is  proved  by  the  fact  that  several  indurated  chancres  resulting  from 
a  single  infection  may  appear  successively  in  the  same  individual 
at  intervals  of  several  days.  The  same  variations  are  observed  in 
gonorrhea.  The  average  is  from  two  to  five  days,  but  the  discharge 
sometimes  sets  in  after  twenty-four  hours  or  appears  very  tardily  at 
the  end  of  several  weeks.    In  the  latter  instance  it  is  assumed  that  the 


EVOLUTION  OF  INFECTIOUS  DISEASES.  407 

microbes  deposited  in  the  balanopreputial  furrow  have  n' »i  invaded 
the  urethra  until  a  certain  time  ofter  coitus.     With  the  Bofl  chancre 
incubation  is  more  fixed  and  does  no1  exceed  twent)  four  ho 
This  figure  is  confirmed  by  numerous  inoculation!  practised  upon 
subjects  presenting  suspicious  ulcerations. 

[nformation  is  quite  precise  in  ca  e  of  infection  of  traumatic 
origin.  In  the  case  of  tetanus  the  period  of  incubation  is  from  two 
to  three  days;  iii  the  statistics  of  the  civil  wax  in  Americi 
find  that  in  twenty-seven  cases  the  aymptome  appeared  on  the 
day  of  traumatism.  Bertran  (of  Elbeuf)  has  seen  tetanut  appear  five 
hours  after  the  infection  of  the  wound.  It  has  been  stated  thai 
incubation  at  times  lasted  only  two  hours.  On  the  other  hand,  \i 
has  in  some  eases  been  prolonged  thirty  and  thirty-five  da] 

In  hydrophobia  the  incubation  period  is  still  more  variable,  the 
average  being  thirty  days  and  the  minimum  fourteen.  As  to  the 
maximum,  a  period  of  eighteen  months  has  been  admitted,  although 
there  are  certain  rare  instances  in  which  the  period  of  incubation 
lasted  two,  three,  and  even  four  years.  Erysipelas  may  be  considered 
as  occupying  a  position  between  traumatic  diseases  and  those  appar- 
ently spontaneous.  Most  of  the  classic  treatises  fix  its  period  of 
incubation  at  three  or  four  days,  admitting  that  it  may  be  reduced 
to  two  days  or  prolonged  to  twelve.  Leaving  aside  the  cases  of  non- 
traumatic erysipelas,  the  beginning  of  which  cannot  be  determined 
with  accuracy,  let  us  consider  the  results  obtained  in  eases  in  which 
streptococcic  infection  developed  in  a  wound.  In  eighty-three  cases 
we  obtained  accurate  information  permitting  us  to  fix  the  time 
elapsing  between  the  accident  and  the  beginning  of  the  infection. 
The  figures  are  as  follows: 

Incubation  period  from 


3  hours 

1 

observation. 

7  to  18      " 

11  observations. 

24      " 

14 

" 

2.5  to  48      " 

11 

" 

40  to  72      " 

9 

'* 

4  to    5  day~ 

s 

•• 

6  to    8     " 

16 

•• 

9  to  15     " 

17 

■• 

111  twelve  cases  incubation  was.  as  we  see.  extremely  short:  not 
the  slightest  doubt  may  be  entertained  as  to  the  evolution,  the 
details  of  the  facts  being  given.     Here  is.  for  example,  one  of  them: 

The  wife  of  a  physician  was  preparing  to  go  to  a  ball.  Inputting 
on  her  ear-rings,  which  she  had  not  worn  for  a  long  time,  she  pro- 

32 


498  INFECTIOUS  DISEASES. 

duced  a  slight  abrasion  in  the  ear.  This  occurred  at  9  p.m.  On  her 
return  home,  at  4  a.m..  she  was  taken  with  a  violent  chill,  fever  set 
in.  and  her  husband  noticed  in  the  morning  the  development  of  a 
typical  erysipelas.  General  reaction  was,  therefore,  produced  seven 
hours  after  traumatism. 

When  erysipelas  develops  tardily  it  may  be  questioned  whether  it 
is  truly  a  case  of  prolonged  incubation,  since  it  is  possible  that  the 
wound  may  be  infected  later  and  that  the  streptococcus  may  not 
have  been  introduced  at  the  moment  of  the  accident.  We  must 
acknowledge  that  the  problem  cannot  be  solved  by  clinical  obser- 
vation alone.  Experimentation  must,  therefore,  be  resorted  to.  If 
we  inoculate  a  culture  of  streptococcus  beneath  the  skin  of  the  ear 
of  a  rabbit,  erysipelas  develops  generally  within  twenty-four  or  forty- 
eight  hours.  At  times  the  incubation  lasts  three  or  four  days.  In 
two  cases  the  author  has  seen  it  prolonged  eleven  days.  Here,  there- 
fore, are  results  of  considerable  practical  consequence.  They  confirm 
what  is  taught  by  clinical  observation  and  establish  that  in  erysipelas 
incubation  may  last  only  a  few  hours  or  exceed  a  week.  But  what 
must  we  think  of  the  cases  in  which  the  period  of  incubation  lasts 
fifteen  or  even  twenty-two  days?  All  hypotheses  are  permitted. 
When,  however,  the  wound  does  not  seem  to  have  been  contaminated 
ulteriorly,  we  may  assume  that  it  was  infected  as  soon  as  it  was 
produced,  whether  the  microbe  proceeded  from  the  soil  or  from 
the  skin  of  the  patient.  Later  on  some  occasional  cause,  which  may 
often  escape  notice,  favors  the  development  of  the  dormant  germs. 
The  influence  of  cold  or  a  draught  in  such  cases  is  thus  explained. 
We  had  a  demonstration  of  this  in  several  cases  in  which  we  saw  a 
recurrence  under  such  influences.  Patients  who  seemed  to  be  com- 
pletely cured  of  erysipelas  left  our  wards,  suddenly  exposed  them- 
selves to  cold,  and  in  the  evening  of  the  following  day  the  infection 
reappeared  and  forced  them  to  return  to  the  hospital.  In  such 
instances  the  microbes  which  still  persisted  in  the  skin  were  exalted 
owing  to  transitory  weakening  of  the  tissues,  occasioned  by  an  auxil- 
iary cause,  however  common  this  cause  may  seem  to  be. 

There  is  another  question.  Is  there  any  relation  between  the 
duration  of  the  period  of  incubation  and  the  gravity  of  erysipelas? 
Our  observations  compel  us  to  answer  in  the  negative.  In  one  of 
the  patients  who  died  the  incubation  period  lasted  eight  days.  In 
two  instances  erysipelas  was  grave,  followed  a  wandering  course,  and 
was  prolonged  for  three  weeks.    In  one  of  these  cases  incubation  had 


EVOLUTION  OF  INFECTIOUS  DISEASES.  ifiit 

lasted  twelve  hours,  in  the  other  eighl  days.  On  the  other  band, 
we  have  seen  ;i,  slight  erysipelas  which  la  ted  only  four  days  and  the 
incubation  period  of  which  did  no1  exceed  thirty-five  hours.  In  fact, 
the  duration  of  the  period  of  incubation  may  be  very  short  in  two 
quite  different  cases.  At  times  evolution  is  grave,  because  the 
microbe  is  highly  virulenl  anddevelopi  withgreai  rapidity.  In  other 
instances,  on  the  contrary,  the  phenomena  appear  speedily  bee 
the  organism  is  capable  of  powerful  reaction.     In  1  hi   case  erysipelas 

is  of  a  more  benign  characlcr  th.'in  if  (he  incubation  had  lasted  longer; 
the  germicidal  serum  and  phagocytes  arrive  early  and  more  easily 
overcome  the  microbes  which  ;uv  ;i  I  ready  developed.  The  explana- 
tion we  propose  is  not  a  mere  hypothesis;  it  is  supported  by  experi- 
mental data.  We  have  shown,  for  example,  that  it  is  possible  to 
shorten  considerably  the  period  of  incubation  by  sectioning  the  vaso- 
motors distributed  to  the  inoculated  ear.  Under  these  renditions 
the  responsive  sensitiveness  of  the  operated  side  is  increased  and 
erysipelas  develops  more  rapidly  than  on  the  normal  side.  But  its 
evolution  is  more  prompt  and  favorable  in  so  far  as  the  lesions,  which 
are  often  observed  in  animals  in  consequence  of  the  streptococcic 
inoculation,  do  not  appear.  Thus,  in  cases  in  which  the  disease  is 
unavoidable  it  is  desirable  that  it  should  begin  early,  since  the 
organism  will  then  combat  a  smaller  number  of  microbes  and  will  be 
less  profoundly  impregnated  by  toxins. 

Among  the  eruptive  fevers,  precise  information  is  most  easily 
obtained  in  smallpox.  Its  period  of  incubation  is,  on  an  averages 
twelve  days,  but  it  may  vary  between  seven  and  fifteen.  In  scarla- 
tina, Sevestre  finds  an  almost  invariable  average  of  four  to  five  days, 
but  there  are  observations  recorded  in  which  the  period  of  incuba- 
tion lasted  no  longer  than  twenty-four  (Trousseau),  twelve  (Seves- 
tre), and  even  seven  hours  (Thomas).  In  other  cases  it  has  been 
prolonged  to  twelve,  seventeen,  and  forty  days  (Rilliet  and  Barthez). 
In  two  instances  reported  by  Dechambre  it  lasted  seven  weeks.  It 
is  well  to  note  that  these  extreme  figures  are  altogether  exceptional 
and  that  an  incubation  period  of  from  two  to  five  days  answers  fairly 
well  to  general  facts.  We  have  been  able  to  establish  the  period  of 
incubation  in  twelve  cases.  In  two  of  these  it  did  not  exceed  twenty- 
four  hours.  One  of  the  two  observations  was  very  precise.  It  was 
the  case  of  a  man  who  had  seen  a  friend  on  his  fifth  day  oi  scarlatina. 
On  the  following  day  he  experienced  fever  and  dysphagia,  and  the 
next  day  the  eruption  appeared.     The  incubation  period  was  forty- 


500  INFECTIO  US  DISEASES. 

eight  hours  in  six  cases  and  three  days  in  another.  Finally,  three 
women  manifested  the  first  symptoms  of  scarlatina  in  sixty-eight, 
seventy,  and  seventy-two  hours,  respectively,  after  having  been 
admitted  as  nurses  to  our  scarlatina  wards.  In  surgical  and  puer- 
peral scarlatinas  the  incubation  period  may  be  very  short,  and 
generally  does  not  exceed  three  days  (Paget,  Sorensen).  This  may, 
perhaps  be  explained  by  the  fact  that  surgical  or  obstetrical  trau- 
matism diminishes  the  resistance  of  the  organism. 

The  incubation  period  of  measles  is  from  eight  to  twelve  days, 
with  a  minimum  of  four  and  a  maximum  of  fourteen.  That  of 
rubeola  is  eighteen  days,  being  sometimes  prolonged  to  twenty  or 
twenty-one,  and  exceptionally  falling  to  eight  and  even  five  days 
(Griffiths).  Varicella  is  said  to  begin  fourteen  to  fifteen  days  after 
contamination.  At  times  it  appears  after  the  nineteenth  day,  but 
never  before  the  thirteenth.  In  two  personal  observations  the 
period  of  incubation  seemed  to  be  seventeen  days.  According  to 
Steiner,  inoculated  varicella  begins  on  the  sixth  clay. 

Of  other  infections  the  incubation  period  of  which  has  been  fairly 
well  determined,  we  may  mention  diphtheria,  which  begins  two  days 
after  contagion,  and  at  times  after  seven  and  even  fifteen  days 
(Sanne);  and  whooping-cough,  from  two  to  eight  clays  after.  In 
mumps  the  incubation  period  is  generally  fifteen  clays.  In  three 
cases  published  by  Roth  it  was  exactly  eighteen  days.  In  cholera 
the  beginning  has  at  times  occurred  a  few  hours  after  contagion.  In 
other  cases  it  has  appeared  on  the  sixth  day.  In  typhus  fever  an 
incubation  period  of  twelve  days  is  generally  admitted,  which  may 
at  times  be  prolonged  to  twenty-three.  The  attack  has  at  times 
occurred  almost  instantly  (Marsh,  Netter).  In  such  cases  individuals 
who  approach  a  patient  are  deeply  impressed  by  a  disagreeable  odor 
and  are  immediately  forced  to  lie  down.  The  following  table,  which 
indicates  the  average,  maximum,  and  minimum  incubation  periods, 
is  based  upon  facts  recorded  by  various  authorities,  upon  statistics 
published  by  Williams  on  behalf  of  a  London  commission,  and  upon 
our  own  personal  observations: 


EVOLUTION  OF  INFECTIOUS  DISEASES. 


601 


Iniiiii  iTIO 

Avi  riii/i 

Minimum. 

Iforimum 

Anl  hrax, 

2  < 

laj             I 

da 

:'. 

days. 

Bubonic  plague, 

1 

lo 

8 

"              2 

•  l:i 

7 

a 

<  Ihanore  (soft), 

1 

lo 

2 

i 

day 

3 

" 

( Iholera, 

'2 

to 

1 

I 

" 

8 

" 

l  )iplii  heria, 

2 

"               2 

da 

15 

" 

Erysipelas, 

1 

to 

(i 

3 

hours 

22 

" 

1  afluenza, 

3 

to 

4 

1 

day 

:. 

" 

< Handera, 

3 

to 

r, 

"            24 

hours 

3 

IIIOIll  I 

<  lonorrhea, 

3 

lo 

5 

I 

(?)    to 

2  daj 

l 

'.il  nreeks. 

Mumps, 

\r, 

7 

da  ■ 

30 

flays. 

Malaria, 

6 

lo 

LO 

"             99 

noun 

Several  months, 

Recurrent  fever, 

5 

to 

6 

"             86 

*t 

S 

days. 

Measles, 

9 

•1 

da] 

14 

a 

1  [ydrophobia, 

20 

to 

on 

13 

" 

L8montb 

Rubeola, 

is 

ft 

" 

21 

days. 

Scarlatina, 

2 

to 

5 

7 

hours 

7 

v.  eel 

Smallpox, 

12 

7 

days 

16 

Syphilis, 

20 

to 

30 

LO 

" 

50 

" 

Tetanus, 

2 

to 

3 

"                 2 

hours 

35 

" 

Typhoid  fever, 

14 

"                2 

days  (?) 

21 

" 

Typhus, 

12 

i) 

(?) 

23 

" 

Vaccinia, 

3 

"                2 

days 

7 

" 

Varicella, 

14 

to 

15 

L3 

" 

19 

" 

Whooping-cough, 

8 

"                2 

" 

8 

" 

Yellow  fever, 

o 

to 

4 

2 

" 

6 

" 

To  the  infections  presented  in  the  foregoing  list  we  may  add  those 
the  microbes  of  which  may  remain  for  a  long  period  of  time  in  a 
latent  state  in  the  organism.  Such  is  the  case  in  tuberculosis  and 
leprosy.  The  most  extraordinary  observation  is  that  of  Hallopeau : 
An  individual  presented  the  first  symptoms  of  leprosy  thirty-two 
years  after  having  returned  from  a  country  where  this  disease  is 
endemic. 

Clinical  experience  suffices  to  establish  that  the  duration  of  the 
incubation  period  is  very  variable,  and  experimental  researches 
have  demonstrated  certain  causes  which  precipitate  or  delay  the 
beginning  of  a  disease.  First,  there  is  an  idea  which  should  never 
be  lost  sight  of,  that  is,  the  variability  in  the  action  of  viruses. 
Viruses  may  be  divided  into  two  groups — i.  e.,  fixed  and  variable. 
In  this  regard  nothing  is  so  instructive  as  the  history  of  hydrophobia. 
The  variable  virus  is  that  found  in  an  animal  which  has  accidentally 
become  rabid.  The  fixed  virus  is  that  which  has  acquired  a  deter- 
mined degree  of  power  by  virtue  of  successive  passages  through  ani- 
mals. By  inoculating  the  virus  into  animals  of  the  same  species 
placed  under  the  same  conditions  the  phenomena  are  produced  after 


502  INFECTIO  US  DISEASES. 

the  lapse  of  a  perfectly  determined  period  of  time.  Such  is  not  the 
case,  however,  in  nature,  and  the  constant  variations  in  virulence 
result  in  modifications  in  the  period  of  incubation.  The  same  result 
is  observed  in  man.  By  virtue  of  its  transmission  by  successive 
inoculations,  vaccinia  has  become  a  fixed  virus.  Its  period  of  incu- 
bation is  almost  invariable.  In  subjects  vaccinated  for  the  first 
time,  the  eruption  appears  seventy-two  hours  after  inoculation,  and 
is  well  developed  in  the  course  of  the  fourth  day.  Even  with  this 
fixed  virus,  however,  certain  variations  are  observed. 

The  soft  chancre,  which  is  transmitted  by  direct  inoculation 
just  as  is  an  experimental  virus,  has  also  acquired  a  sufficiently 
fixed  power.  Hence,  the  lesion  always  begins  twenty-four  or 
forty-eight  hours  after  contamination.  The  occurrence  of  a  longer 
period  of  incubation  must  be  attributed  to  inaccurate  observa- 
tion. 

It  can  readily  be  understood  that  with  viruses  of  variable  potency 
the  greater  the  energy  and  number  of  microbes  introduced  the 
shorter  will  be  the  incubation  period.  The  period  of  incubation 
will  also  vary  with  the  location  of  the  wound.  It  will  be  longer 
if  the  affected  region  is  provided  with  dense  cellular  tissue  and  is 
poorly  supplied  with  vessels  and  nerves.  Such  is  strikingly  the  case 
in  hydrophobia.  Finally,  microbes  develop  more  readily  when 
they  are  introduced  simultaneously  with  irritating  substances  or 
other  bacteria,  even  simple  saprophytes,  favoring  their  multipli- 
cation. 

On  the  part  of  the  organism  all  causes  of  weakening  should  be 
taken  into  account — extensive  traumatism,  laceration  of  tissues, 
modifications  of  the  general  condition  by  overexertion,  excesses, 
alcoholism,  intoxications,  and  previous  or  present  diseases.  Lastly, 
we  must  not  overlook  the  influence  of  moral  impressions,  the  power 
of  which  is  well  known  with  respect  to  hydrophobia.  For  example, 
an  individual  who  has  been  bitten  by  a  rabid  animal  no  longer 
thinks  of  his  accident.  Suddenly  a  word  reminds  him  of  the  bite, 
and  immediately  manifestations  of  the  disease  appear  and  rapidly 
terminate  in  death.  The  duration  of  the  period  of  incubation  may 
also  be  modified  by  the  responsive  aptitudes  of  the  subject.  In 
persons  with  very  sensitive  nervous  systems  the  onset  will  be 
hastened.  In  this  particular  case  a  short  period  of  incubation 
constitutes  a  favorable  phenomenon. 


EVOLUTION  OF  INFECTIOUS  DISEASES.  503 

Invasion. 

Invasion  may  be  sudden,  or  slow  and  progresi  ive.  In  the  former 
instance  the  stationary  period  i  quickly  reached)  in  the  latter  il 
supervenes  only  at  the  end  of  a  f<-w  days,  and  is  thus  preceded  by 
a  prodromic  period  in  which  the  symptom  are  inadequate  to 
determine  the  nature  of  the  morbid  proce 

As  an  example  of  infection  with  sudden  unci,  writers  alv 
cite  pneumonia,  and,  as  an  example  of  slow  invasion,  typhoid  fever. 
These  two  illustrations  are  well  chosen.  Clinical  phenomena  are 
always  so  variable,  however,  thai  a  greal  many  exceptions  may  be 
mentioned.  There  are  cases  of  pneumonia  beginning  in  a  Blow  and 
insidious  manner,  and  I  here  are  typhoid  fevere  characterized  by  a 
sudden  onset.  It  is  not  difficult  to  understand  how  progressive 
invasion  is  effected.  The  noxious  substances  are  secreted  little  by 
little  by  the  microbes,  become  diffused  in  the  organism,  and  influence 
the  cells.  When  the  toxins  are  elaborated  in  greater  amount  their 
constantly  increasing  accumulation  gives  rise  to  more  and  more 
marked  disturbances.  A  sudden  onset  is  more  difficult  of  explan- 
ation. Even  in  pneumonia  it  is  possible  that  the  morbid  poison  is 
secreted  in  a  progressive  mariner,  and  at  first  sight  the  sudden 
appearance  of  the  phenomena  is  not  understood.  The  differences 
are  probably  due  to  the  mode  of  action  of  poisons.  This  view  i-. 
of  course,  purely  hypothetical,  but  it  is  supported  by  some  facts. 
A  first  result  which  must  be  taken  into  account  is  that  most  microbic 
toxins,  unlike  poisons  properly  so  called,  and  notably  alkaloids, 
exert  no  immediate  action.  Even  when  they  are  introduced  into 
the  blood  no  immediate  symptom  is  produced,  but  after  a  period 
of  latency  of  varying  duration  the  morbid  phenomena  suddenly 
appear.  This  experimental  fact  has  a  very  important  bearing  upon 
our  subject.  In  fact,  it  may  be  assumed  that  in  certain  cases 
microbic  poisons  act  clearly  and  rapidly  as  they  are  elaborated. 
Under  such  conditions  disturbances  begin  slowly  and  follow  a  pro- 
gressive course.  In  other  instances  an  oversaturation  of  the 
organism  will  be  required  in  order  to  produce  reaction.  This  is  the 
first  effect  of  cumulative  doses. 

Whatever  be  the  mode  of  invasion,  the  general  phenomena  first 
bear  on  the  nervous  system.  If  invasion  is  slow  and  progressive, 
the  disturbances  are  gradually  intensified.  These  are  malaise,  head- 
ache, dizziness,  weakness  of  the  extremities,  and  incapacity  for  all 


504  ISFECTIO  US  DISEASES. 

muscular  or  mental  exertion.  Delirium,  if  present,  is  of  the  mild, 
quiet  type.  Sleep  is  disturbed  only  by  nightmares  or  some  vagaries. 
On  the  whole,  the  symptoms  are  not  intense,  and  are  established 
gradually  and  aggravated  in  a  slow,  and  often  regular,  manner. 
On  the  other  .hand,  if  invasion  is  sudden  the  nervous  symptoms 
will  be  intense  and  disquieting  from  the  first.  The  process  is  of  the 
nature  of  a  true  outbreak.  There  has  been  a  silent  accumulation 
of  toxins,  and  all  of  a  sudden  a  violent,  impetuous,  unexpected 
reaction  occurs — i.  e.,  intense  chills  or,  in  children,  a  convulsive 
attack.  At  the  same  time  fever  develops  and  rapidly  reaches 
102.2°    or  104°    F.  (39°    or  40°    C). 

Headache  is  intense,  and  delirium  may  be  excessive  from  the  first. 
Severe  delirious  phenomena  are  mostly,  we  might  say  nearly  always, 
observed  in  diseases  characterized  by  sudden  onset  and  occurring 
in  predisposed  individuals.  Delirium  tremens  is  altogether  excep- 
tional in  typhoid  fever.  It  is  not  so  rare  in  smallpox  and  erysipelas, 
but  it  is  especially  frequent  in  pneumonia.  It  expresses  a  profound 
nervous  perturbation,  and  occurs  in  alcoholic  subjects  as  a  result  of 
the  toxomicrobic  shock,  as  is  sometimes  produced  by  violent  trau- 
matism. 

In  diseases  characterized  by  sudden  invasion,  a  series  of  symptoms 
which  might  be  connected  with  visceral  lesions,  but  which  seem  to 
be  dependent  upon  disturbance  of  innervation,  is  observed  from  the 
very  beginning.  These  are,  vomiting  without  any  apparent  altera- 
tion of  the  stomach ;  diminution  in  the  quantity  of  urine,  at  times 
transitory  suppression,  without  the  kidneys  as  yet  being  affected; 
intense  dyspnea,  unexplained  by  the  condition  of  the  lungs,  and 
acceleration  of  the  pulse  and  arrythmia,  which  are  in  nowise  de- 
pendent upon  cardiac  lesions.  There  is  a  striking  discord  between 
the  functional  and  the  anatomical  conditions. 

Thus  far  we  have  considered  only  those  cases  in  which  invasion 
is  announced  by  general  phenomena.  In  other  cases,  infectious 
diseases  may  begin  with  local  manifestations,  which  at  times  precede, 
sometimes  accompany,  the  general  reactions,  and  sometimes  they 
run  their  course  without  giving  rise  to  any  general  phenomena.  In 
certain  cases,  however,  the  local  lesions  develop  very  rapidly.  This 
occurs  in  young  subjects  endowed  with  a  nervous  system  which 
reacts  quickly  and  with  energy,  for  example,  in  children  attacked 
by  acute  pulmonary  congestion.  The  child  is  suddenly  taken  by 
fever,  and  auscultation  practised  immediately  reveals  an  intense 


EVOLUTION  OF  INFECTIOUS  DISEASES. 

blowing  murmur.     Everything  is  again  normal  on  the  following 
day.    The  fever  has  subsided,  and  the  murmur  i    no  longer  per- 
ceptible.   These  fuels,  which  have  been  so  well  studied  by  Bergeron, 
Cadet  de  (Jnssieourt,  and  llime,  musl  !«•  considered  a   example 
true  abortive  pneumonias. 

Immediately  upon  its  arrival  the  microbe  gives  rise  to  violenl 
reactions  which  often  resull  in  the  instanl  arrei  I  of  n  course.  The 
excitation  of  the  nervous  system  is  expressed  by  a  congestive  fluxion 
which  arrests  the  infection.  In  the  same  order  of  ideas,  although 
their  meaning  is  more  difficull  to  understand,  we  may  mention 
herpes,  which  is  so  frequently  observed  in  infections,  and  urticaria, 
which  appears  especially  in  cases  of  digestive  disturbances.  Evi- 
dently the  phenomena  <>f  fluxion  are  alone  capable  of  making  a 
sudden  appearance.  The  other  responsive  manifestations  develop 
more  slowly,  and  if  they  at  limes  appear  suddenly  it  Is  bec;m~e 
their  beginning  has  been  effected  in  a  gradual  manner  and,  having 
already  advanced  to  a  certain  degree,  they  suddenly  give  rise  to 
morbid  reactions.  There  is  often  a  lack  of  harmony  between 
general  and  local  manifestations.  In  a  certain  number  of  cases 
the  two  orders  of  symptoms  begin  simultaneously.  In  other.-  the 
disease  is  at  first  characterized  by  one  or  the  other  series  of  symp- 
toms. In  still  other  instances  local  reactions  are  progressive,  while 
general  manifestations  are  abrupt,  and  vice  versa.  There  exist, 
therefore,  a  whole  series  of  different  modes  of  reaction  of  which 
clinical  experience  furnishes  well-known  examples. 

The  same  infection  may  sometimes  start  with  local  manifestations, 
and  at  other  times  by  general  symptoms.  Surgeons  have  empha- 
sized this  fact  in  describing  phlegmons.  They  have  remarked  that 
the  beginning  with  general  reactions  indicates  a  greater  virulence 
of  the  morbid  germ,  and  consequently  a  grave  prognosis.  This 
remark  is  correct,  but  must  not  be  generalized.  In  erysipelas,  for 
instance,  these  two  modes  of  invasion  occur  without  one  being 
more  benign  or  more  serious  than  the  other. 

The  duration  of  the  invasion  period  varies  considerably  according 
to  the  infection  under  consideration,  and  is  not  absolutely  fixed  in 
each  disease.  Authorities  have  endeavored,  however,  to  establish 
averages.  It  is  generally  admitted  that  invasion  lasts  two  days 
in  scarlatina,  three  days  in  measles,  and  from  two  to  five  days  in 
variola.  In  the  latter  infection  short  invasions  are  observed, 
especially    in    grave    cases;  long    invasions    in    benign    forms.     In 


506  IXFECTIO  US  DISEASES. 

erysipelas,  invasion  is  supposed  to  last  from  a  few  hours  to  a  day, 
and  the  maximum  is  fixed  at  two  days. 

These  rules  are  fairly  exact,  hut  they  suffer  a  certain  number  of 
exceptions.  According  to  our  personal  observations  the  classical 
figure  is  observed  in  a  little  more  than  one-third  of  the  cases  of 
measles  in  adults.  In  children  below  two  years  of  age  the  period 
of  invasion  is  generally  very  short.  In  scarlatina  invasion  lasts 
forty-eight  hours  in  half  of  the  cases ;  it  is  not  infrequently  shorter, 
but  seldom  longer.  As  to  variola,  the  law  of  Sydenham,  accepted 
by  Trousseau,  is  well  known.  An  invasion  of  two  days  or  two  days 
and  a  half  indicates  a  confluent  variola;  an  invasion  of  three  days 
and  a  half  or  four  days  and  more  particularly  when  it  lasts  five 
days,  indicates  a  discrete  variola.  Prof.  Jaccoud  has  modified  the 
formula.  He  maintains  that  a  short  invasion  may  be  followed  by 
a  discrete  variola,  but  a  prolonged  invasion  never  precedes  a  con- 
fluent variola,  Our  statistics  show  that  there  are  exceptions  to 
all  these  rules,  and  that  variolas  have  at  times  been  confluent  after 
periods  of  invasion  lasting  four,  five,  and  even  six  days.  Moreover, 
we  have  inquired  as  to  the  applicability  of  Sydenham's  law  as 
modified  by  Jaccoud  to  the  majority  of  cases,  and  we  have  reached 
the  conclusion  that  in  all  forms  of  variola,  excluding  the  primarily 
confluent  variety,  invasion  generally  lasts  three  days.  In  one-third 
of  the  cases  it  does  not  exceed  one  or  two  days.  The  law  of  Syden- 
ham-Jaccoud  is,  therefore,  exact  in  54  per  cent,  of  the  cases. 

Stationary  Period. 

Since  the  time  of  Hippocrates  it  has  been  customary  to  admit 
three  periods  or  stages  in  the  evolution  of  acute  diseases :  an  invading 
period,  a  stationary  period,  and  a  period  of  decline.  Jaumes  has 
proposed  another  division.  He  admits  but  two  periods — i.  e.,  one 
characterized  by  a  morbid  effort  corresponding  to  the  period  in 
which  the  organism  is  overwhelmed,  and  one  occurring  only  in 
favorable  cases,  a  period  of  improvement  and  restoration.  In  other 
words,  the  first  period  corresponds  to  the  attack  of  the  pathogenic 
cause,  and  the  second  to  the  curative  effort  of  the  organism.  This 
division  is  quite  in  harmony  with  the  present-day  conception  of 
disease.  It  would  have  been  perfect  if  reaction  really  followed 
action,  and  if  disease  followed  a  regularly  descending  course  after 
arriving  at  its  height  through  a  progressive  aggravation.  In  reality 
the  facts  are  more  complex.     As  we  have  repeatedly  stated,  the 


EVOLUTION  OF  INFECTIOUS  DISEASES.  607 

defensive  reactions  begin  at  the  same  time  8  the  offensive  action  . 
and  at  times  even  Ik -lore  all  appreciable  ymptom  .  Consequently) 
the  two  classes  of  symptoms  con  tantly  intermingle,  with  the 
exception,  however,  thai  the  pathogenic  agenl  has  the  advantage 
in  the  beginning.  The  reactions  of  the  invasion  period  indicate 
that  the  organism  is  defeated,  of  a1  lea  i  on  the  defensive.  Then 
conies  a  period  when  ihe  si  niggle  assumes  a  seriou  character,  and 
the  two  participants  fully  display  their  forces.  This  i-  the  stationary 
period,  wliieh  a1  limes  seems  io  remain  unchanged,  and  al  others 
a  series  of  deviations  occurs  depending  upon  the  various  vicissitudes 
of  the  struggle.  This  period  is  the  mosl  important  from  a  noso- 
logical standpoint,  since  the  characteristic  symptoms  of  the  disease 
are  fully  developed.  They  ;ire  so  grouped  as  to  constitute  a  special 
type  which  is  easily  defined  and  classified.  It  is  a1  this  moment 
that  a  previously  hesitating  diagnosis  may  be  made  more  certain. 

In  studying  the  stationary  period  the  local  symptoms  and  general 
phenomena  must  likewise  be  taken  into  consideration.  When  the 
local  manifestations  occupy  the  external  pails  they  may  readily 
be  studied.  Such  is  the  case  with  erysipelas,  absce»e<.  ;md  phleg- 
mons, cutaneous  ulcerations  and  gangrenes. 

These  are  also  quite  easily  recognized  when  they  occupy  a  mucous 
membrane  which  is  accessible  to  exploration,  such  as  that  of  the 
mouth  and  pharynx.  In  case  a  deeply  seated  organ  is  attacked, 
the  study  becomes  more  difficult;  yet,  according  to  the  modifications 
manifested  in  the  functions  of  the  organ  and  the  changes  which 
may  be  perceived  by  means  of  physical  examination,  palpation, 
percussion,  and  auscultation,  we  can  quite  exactly  determine  and 
follow  the  evolution  of  the  phenomena  produced  in  the  deeper  parts 
of  the  economy. 

In  certain  cases,  even  the  minutest  exploration  fails  to  reveal 
any  organic  alteration,  because  the  symptoms  are  of  a  general 
character.  The  latter  consist  in  responsive  manifestations  referable 
chiefly  to  the  nervous  system,  the  secretions,  and  thermogenesis. 
The  nervous  symptoms  are  those  which  have  already  been  noted 
in  treating  of  the  invasion  period — i.  c  headache,  incapacity  for 
work,  a  diminution  of  psychical  acuity,  delirium,  and.  exceptionally, 
convulsions.  The  secretions  are  for  the  most  part  diminished. 
The  urine  is  scanty,  the  saliva  is  not  abundant,  and  the  tongue  is 
dry.  Finally,  thermogenesis  is  also  perverted,  and  there  is  usually 
a  rise  of  both  peripheral  and  central  temperature. 


508  INFECTIOUS  DISEASES. 

A  comparison  of  local  and  general  symptoms  leads  to  the  following 
conclusions:  Sometimes  the  local  and  general  phenomena  follow 
a  parallel  course.  They  are  aggravated  or  improved  simultaneously. 
They  decline  and  disappear  almost  at  the  same  time.  Sometimes 
there  is  a  decided  discord  between  the  two  orders  of  phenomena. 
Thus,  for  instance,  the  local  lesion  may  subside  while  the  general 
phenomena  grow  worse.  In  such  cases  there  is  generally  some 
fresh  complication.  More  frequently  the  reverse  is  the  case.  The 
general  manifestations  vanish,  whereas  the  local  symptoms  seem 
to  remain  stationary.  This  fact  is  particularly  striking  in  pneu- 
monia. From  day  to  da}^  a  sudden  defervescence  takes  place. 
The  temperature,  which  had  risen  to  104°  F.  (40°  C),  falls  to  98.5°  F. 
(37°  C).  The  secretions  are  re-established;  the  patient  experiences 
a  feeling  of  well-being  which  makes  him  realize  that  his  sickness 
is  over,  and  yet  no  improvement  has  taken  place  in  the  condition 
of  the  lung.  On  the  contrary,  the  stethoscopic  signs  are  the  same 
as  the  day  before.  The  same  lack  of  parallelism  is  observed  in 
erysipelas,  but  less  constant^.  The  general  phenomena  subside, 
while  the  cutaneous  lesion  persists  without  any  change.  Finally, 
in  certain  cases  the  discord  is  no  longer  real,  as  in  the  preceding 
examples,  but  only  apparent.  The  local  lesion  seems  to  remain 
unchanged,  and  yet  the  general  phenomena  are  modified  or  even 
aggravated.  These  indicate  either  a  local  change,  which  we  are 
thus  enabled  to  recognize  and  predict,  or  a  new  perturbation, 
perhaps  a  commencing  complication. 

In  order  to  recognize  the  nature,  follow  the  evolution,  establish 
the  prognosis,  and  predict  the  possible  accidents  of  a  disease,  we 
must  at  the  same  time  take  into  account  the  local  and  general 
manifestations  and  their  harmony  or  discordance. 

Let  us  first  consider  the  local  phenomena.  Five  events  are 
possible  • 

1.  The  local  lesion,  which  began  during  the  period  of  invasion, 
is  not  modified  during  the  stationary  period,  but  follows  a  very 
simple  evolution,  increases  gradually,  reaches  its  height,  and  then, 
in  favorable  cases,  resolves.  No  notable  change  in  its  character 
or  aspect  appears.  Of  numerous  illustrations  it  will  suffice  to 
mention  mumps,  erysipelas,  and  gonorrhea.  We  might  add  scarlet 
fever  and  measles,  in  which  the  eruption  characterizing  the  stationary 
period  extends  progressively  to  all  parts  of  the  skin,  but  always 
preserves  an  invariable  aspect. 


EVOLUTION  OF  INFECTIOUS  DISEASES.  609 

2.  In  other  cases  the  local  lei  ion  i  modified  from  day  to  day. 
An  abscess  may  be  taken  as  an  example  in  which  exploration  i-  i 

At  first  induration  is  present,  then  the  lesion  undergoe  softening, 
becomes  fluctuating,  and  opens  exteriorly.  A  like  course  may  be 
observed  in  ruses  of  visceropathies.  In  simple  bronchitis  there  i 
a  period  of  crudity,  when  expectoration  is  difficult  and  painful. 
Then  a  period  of  coction,  when  the  sputa  become  mucopurulent 
and  arc  easily  expectorated.  Examination  of  the  sputa  :i-  well  at 
auscultation  demonstrate  the  changes  characterizing  these  two 
periods.  By  the  same  methods  of  exploration  we  can  follow  per- 
fectly the  evolution  of  a  pneumonic  focus:  In  the  beginning  there 
is  pulmonary  obstruction  resulting  from  the  exudations,  and  auscul- 
tation reveals  crepitant  rales.  Next,  a  fibrinous  exudation  into 
the  air  cells  takes  place;  this  is  the  period  of  red  hepatization, 
characterized  by  tubular  breathing.  Lastly,  the  exudation  softens 
and  auscultation  reveals  rales  of  resolution. 

3.  Instead  of  remaining  localized  in  a  region  the  local  lesion  ex- 
tends and  invades  the  neighboring  parts.  Here  erysipelas  and 
pneumonia  may  again  serve  as  examples.  While  often  circum- 
scribed, erysipelatous  inflammation  sometimes  extends  over  a 
great  part  of  the  skin.  At  times  it  covers  the  entire  surface  of  the 
body.  This  is  a  particular  clinical  form  justly  described  under  the 
name  ambulatory  erysipelas.  The  same  evolution  maybe  observed 
in  the  lungs,  under  which  circumstances  pneumonia  is  designated 
as  migrating.  In  certain,  but  fortunately  very  rare,  instance-  a 
local  lesion  grows  both  deeper  and  larger,  causing  considerable  loss 
of  substance.  This  is  known  as  phagedenism,  and  is  observed 
chiefly  in  the  soft  chancre,  which  lesion  may  destroy  the  penis, 
invade  the  scrotum  and  thighs,  and  follow  a  serpiginous,  extensive 
course,  the  duration  of  which  may  be  months  or  even  years. 

4.  The  local  lesion  sometimes  progresses  by  successive  st:  s  - 
When  the  lesion  seems  on  the  point  of  subsiding,  or  has  even  disap- 
peared, arecidive  sometimes  occurs  in  the  region  primarily  attacked. 
This  is  observed  especially  in  erysipelas.  In  other  instances  the 
recurrence  takes  place  in  parts  more  or  less  distant  from  the  region 
primarily  diseased,  for  example,  orchitis,  occurring  in  mumps,  and 
endocarditis,  pericarditis,  or  meningitis  in  pneumonia.  The  patho- 
genic agent  thus  tends  to  colonize  distant  tissues  or  organs.  The 
process  is,  as  it  were,  a  relapse  at  a  distance.  In  a  certain  number 
of  cases  the  appearance  of  a  new  morbid  focus  coincides  with  the 


510  INFECTIO  US  DISEASES. 

disappearance  of  the  primary  focus.  This  is  metastasis,  the  best 
illustration  of  which  is  furnished  by  the  history  of  rheumatism": 
when  cerebral  manifestations  appear  the  swelling  in  the  articula- 
tions subsides,  the  pain  disappears,  sometimes  with  astonishing- 
rapidity:  a  transfer  of  the  fluxion  from  the  articulations  to  the 
nervous  centres  occurs. 

5.  The  local  lesion  may  be  modified  by  an  additional  infection. 
Pathogenic  microbes  implanting  themselves,  for  example,  in  a  part 
already  diseased,  give  rise  to  suppuration,  and  may  even  invade 
the  economy.  In  gonorrhea  the  gonococcus  often  remains  localized 
in  the  urethra.  Common  bacteria,  however,  soon  join  it,  and  may 
subsequently  induce  very  serious  disturbances.  Although  the  gono- 
coccus may  at  times  invade  the  organism,  the  so-called  gonorrheal 
rheumatism  generally  depends  upon  ordinary  pyogenic  bacteria. 
The  process  is  one  of  attenuated  purulent  infection  to  which  the 
agent  of  gonorrhea  has  merely  opened  the  way. 

General  phenomena  usually  follow  a  course  parallel  to  that  of 
local  symptoms.  During  the  stationary  period  they  may  remain 
quite  unmodified.  In  pneumonia,  for  instance,  the  fever  remains 
about  104°  F.  (40°  C).  Dyspnea,  thirst,  and  headache  remain 
about  the  same  during  the  entire  evolution.  The  same  remark 
holds  true  of  typhoid  fever,  although  some  differences  are  revealed 
by  a  more  careful  study. 

In  some  instances  the  general  symptoms  are  modified  several 
times,  so  that  the  stationary  period  has  been  divided  into  a  certain 
number  of  secondary  periods.  In  other  cases  the  general  phenomena 
keep  pace  with  the  local,  as  is  observed  in  smallpox.  Sometimes 
the  changes  do  not  seem  to  harmonize.  Thus,  in  tubercular  menin- 
gitis three  periods,  which  apparently  do  not  correspond  to  ana- 
tomical changes,  have  been  described  according  to  the  general 
symptoms.  After  a  phase  characterized  by  violent  headache,  fever, 
constipation,  and  vomiting,  a  marked  remission  occurs,  which  lasts 
nearly  a  week.  The  patient  is  believed  to  be  convalescent,  when  the 
symptoms  reappear  and  go  from  bad  to  worse,  ending  in  death. 

In  a  certain  number  of  infections  the  modifications  in  the  general 
phenomena  express  the  generalization  of  a  primarily  local  microbic 
process.  Such  is  the  case  with  malignant  pustule.  The  lesion  is  at 
first  characterized  simply  by  a  cutaneous  eschar.  In  certain  cases 
phenomena  of  general  infection  are  subsequently  produced,  indicat- 
ing the  invasion  of  the  economy  by  the  pathogenic  agent.    Likewise, 


EVOLUTION  OF  INFECTIOUS  DI8EA8ES.  :,|  | 

in  cases  of  septicemia  or  pyemia  consecutive  to  local  le  ions,  the 
changes  occurring  in  the  general  symptom  reveal  the  invasion  of 
the  organism. 

Nosologists  have  divided  the  stationary  period  r>i  di  i 
taking  into  accounl  both  the  modifications  occurring  in  the  local 
symptoms  and  the  general  manifestations.  Undoubtedly  these 
divisions  are  not  always  perfect.  Didactic  description!:  are  tn 
sarily  schematic  and  cannot  give  an  exacl  idea  of  the  complexity 
of  clinical  phenomena.  We  have  above  referred  to  tubercular 
meningitis.  Its  evolution  in  three  phases,  admitted  by  all  classical 
treatises,  is,  however,  of  rare  occurrence.  The  phenomena  very 
seldom,  if  ever,  progress  with  such  quasi-mathematical  precision  as 
has  been  attributed  to  them.  The  clinical  types  are,  in  reality, 
far  more  complex  and  variable  than  may  be  supposed  from  classical 
descriptions. 

The  general  phenomena  have  been  divided  into  continued,  re- 
mittent, intermittent,  and  irregular,  mainly  upon  the  basis  of  the 
precise  data  of  medical  thermometry.  After  the  details  which  we 
have  given  in  treating  of  the  febrile  process  (p.  355),  it  will  suffice  to 
say  that  general  morbid  manifestations  run  a  course  nearly  parallel 
to  that  of  fever,  increasing  or  diminishing  with  it,  and  thus  present- 
ing the  same  daily  variations.  There  are,  however,  exceptions  to 
this  rule.  There  may  be  dissociation  between  the  two  order.-  of 
phenomena.  Febrile  manifestations  may  diminish  while  the  other 
symptoms  become  aggravated.  Such,  for  instance,  is  the  case  in 
hepatic  or  renal  lesions.  We  have  then  to  deal  with  particular 
clinical  forms. 

Clinical  Forms.  The  stationary  period  of  infectious  diseases  being 
the  longest  and  especially  the  best  characterized,  has  served  to 
differentiate  clinical  types.  On  the  basis  of  their  evolution  cyclic 
diseases  may  be  admitted  in  which  the  duration  is  sufficiently 
defined  and  determined  by  a  regular  succession  of  morbid  phenom- 
ena. Pneumonia,  typhoid  fever,  and  eruptive  fevers  belong  to 
this  category.  It  should  be  remembered,  however,  that  the  figures 
given  by  authorities  are  subject  to  numerous  variations.  The  term 
of  nine  days  assigned  to  pneumonia,  and  of  three  weeks  To  typhoid 
fever,  represent  averages  which  are  seldom  realized.  Nevertheless, 
the  term  may  be  retained  in  contradistinction  to  non-cyclic  dis«  -  s 
such  as  diphtheria  and  erysipelas,  whose  capricious  course  defies  all 
efforts  at  averaging.     Even  in  those  diseases  in  which  the  stationary 


512  INFECTIOUS  DISEASES. 

period  is  best  determined  very  great  variations  may  be  observed. 
In  certain  cases  the  evolution  is  shortened,  either  because  the  disease 
assumes  a  very  acute,  speedy  course,  causing  death  very  rapidly,  or, 
on  the  contrary,  because  it  follows  an  abortive  course.  Pneumonia 
is  again  a  good  illustration.  This  infection  may  kill  at  times  within 
a  few  hours,  as  occurs  in  the  aged,  in  diabetics,  and  in  individuals 
suffering  from  previous  diseases,  notably  erysipelas.  In  this  con- 
nection we  may  also  mention  the  speedy  types  of  scarlatina,  small- 
pox, and  cholera.  Death  may  supervene  at  the  beginning  of  the 
stationary  period,  and  even  before  the  latter  is  clearly  established. 

Pneumonia  likewise  furnishes  the  best  illustration  of  an  abortive 
infection.  The  disease  begins  suddenly,  reaches  the  stationary 
period,  and  all  at  once  defervescence  occurs  on  the  third  or  fourth 
day.  Abortive  typhoid  fevers  have  also  been  described,  and  we  may 
likewise  admit  the  occurrence  of  abortive  eruptive  fevers — i.  e., 
such  as  are  cut  short  after  a  prodromic  period.  Thus,  an  individual 
who  has  been  exposed  to  the  contagion  of  variola  is  seized  with  all 
the  premonitory  symptoms  of  this  disease;  then  the  symptoms 
disappear  and  the  eruption  is  characterized  by  two  small  pustules. 
This  is  evidently  an  instance  of  an  attack  of  variola  deserving  the 
name  abortive.  Notwithstanding  the  intensity  of  the  symptoms  of 
invasion,  the  disease  is  cut  short.  Cases  of  abortive  erysipelas, 
which  stop  suddenly  after  the  period  of  invasion,  at  the  very  begin- 
ning of  the  stationary  period,  may  also  be  admitted.  It  is  useless  to 
multiply  examples.  While  these  facts  are  already  well  known,  the 
author  believes  them  to  be  far  more  frequent  than  is  usually  supposed. 
Many  febrile  paroxysms,  transitory  indispositions,  and  sudden  chills, 
which  are  followed  by  no  special  manifestations  whatever  and  which 
run  their  course  in  a  day  and  sometimes  in  a  few  hours,  are  to  be 
accounted  for  by  an  infection  that  is  abortive.  Consecutive  to 
infections  occurring  during  convalescence  from  eruptive  fevers  or 
erysipelas,  we  often  see  febrile  paroxysms  which,  apparently,  are 
referable  to  no  other  cause.  This  is  demonstrated  by  the  fact  that 
numerous  transitions  are  observed  between  the  ephemeral  fevers, 
which  can  in  nowise  be  accounted  for,  and  those  which  indicate 
relapse  or  a  complication. 

By  the  side  of  diseases  aborting  spontaneously  should  be  placed 
those  aborting  in  consequence  of  therapeutic  intervention.  Cases 
of  this  kind,  formerly  rare,  will  become  more  and  more  frequent  as 
we  become  better  acquainted  with  specific  medication.     The  latter 


EVOLUTION  OF  INFECTIOUS  DISEASES.  :,|:; 

is  sometimes  represented  by  vegetable  or  mineral  producl  .  Such 
are  the  salts  of  quinine,  whirl:  arrest  malarial  infection,  and  the 
salts  of  silver,  which  stop  ;i  beginning  gonorrhea,  and  especially  the 
preparations  of  mercury,  which  suspend  the  evolution  ol  syphilis. 
At  present  specific  and  abortive  remedies  are  looked  for  in  Bub- 
stances  derived  from  immunized  animal  .  The  results  obtained  by 
serum  therapy  inspire  us  wild  the  hope  thai  the  time  is  nol  far 
distant  when  it  will  be  possible  i"  arresl  the  evolution  of  a  ■. 
number  of  infectious  diseases. 

The  acute  infections,  even  when  they  generally  follow  ;i  cyclic 
course  and  terminate  within  a  well  determined  time,  may  in  some 
cases  be  prolonged  beyond  the  usual  limits.  For  instance,  pneu- 
monia, instead  of  lasting  nine  days,  may  not  reach  defervescence 
until  toward  the  twelfth  or  even  the  fifteenth  day.  Likewise, 
typhoid  and  eruptive  fevers  are  nol  infrequently  prolonged  in  an 
unusual  manner,  although  examination  of  the  patienl  fails  to  explain 
the  persistence  of  the  morbid  symptoms.  There  is,  bo  to  say,  a 
torpidity  of  the  organism  which  fails  to  produce  the  special  con- 
ditions capable  of  arresting  the  infection. 

In  a  great  number  of  cases,  however,  prolongation  of  the  cha 
is  clue  to  a  particular  course  or  to  the  influence  of  complications. 
The  evolution  is  prolonged  as  the  result  of  successive  invcu 
At  the  moment  when  the  infection  is  believed  To  have  nearly  termi- 
nated a  new  focus  is  produced.  Pneumonia  and  typhoid  fever  may 
evolve  in  this  manner,  and,  although  the  new  attack  is  generally  of 
shorter  duration  than  the  first,  the  total  duration  is  thereby  con- 
siderably prolonged.  This  mode  of  evolution,  while  rare  in  the 
diseases  above  referred  to.  is  the  rule  in  certain  infections.  Such 
is  the  case  with  recurrent  typhus,  intermittent  fever,  and  varicella, 
the  duration  of  the  last-named  disease  being  extremely  variable  on 
account  of  the  variation  presented  by  the  course  of  successive 
recurrences.  In  certain  cases  the  recidive  of  morbid  symptoms  is 
preceded  by  a  certain  interval  of  recovery.  A  recurrence  is  then 
said  to  have  taken  place.  As  in  the  case  of  relapse,  recurrence  is 
generally  less  grave  than  the  first  attack:  but  this  rule  is  subject 
to  a  great  number  of  exceptions. 

Finally,  morbid  evolution  may  he  prolonged  by  reason  of  com- 
plications occurring  during  the  stationary  period  or  convalescence. 
New  phenomena,  mostly  referable  to  superadded  infections  .[may  thus 
lengthen  the  duration  of  a  disease  for  a  considerable  period  of  time. 

33 


514  ISFECTIO  US  DISEASES. 

It  is  evident  that  nothing;  but  hypotheses  can  be  advanced  as  to 
the  causes  which  intervene  to  abridge  or  prolong  infections.  Aside 
from  those  cases  in  which  secondary  complications  are  responsible, 
it  is  not  understood  why  morbid  action  is  cut  short  and  then  re- 
appears when  defervescence  is  about  to  set  in  or  even  after  con- 
valescence has  began.  The  solution  of  these  problems  is  intimately 
connected  with  the  study  of  predisposition,  immunity,  and  the 
mechanism  of  recovery.  If,  as  is  generally  admitted,  recovery  is 
effected  by  virtue  of  chemical  and  dynamic  modifications  pro- 
duced within  the  organism ;  if  it  is  dependent  upon  an  increase  of 
the  germicidal  power  of  the  tissue  fluids  and  upon  the  phagocytic 
activity  of  the  cells,  the  duration  of  the  disease  will,  of  course, 
depend  upon  the  rapidity  of  the  organic  changes,  namely,  upon  the 
responsive  potency  of  the  economy.  Relapses,  on  the  other  hand, 
would  be  due  to  an  insufficiency  of  reaction.  This  explanation, 
however,  is  inadequate.  What  we  desire  to  determine  are  the  causes 
or  conditions  which  arouse  the  responsive  activity  of  the  economy 
promptly  in  one  case,  slowly  in  another,  and  incompletely  in  a 
third.  The  question  is  thus  reduced  to  a  problem  of  a  much  more 
general  nature.  In  a  very  great  number  of  conditions  morbid  re- 
actions are  observed  which  are  partly  dependent  upon  the  nervous 
system  and  partly  upon  the  state  of  general  nutrition.  These 
reactions  vary  considerably  from  one  subject  to  another,  and  this 
variability  is  connected  with  the  hereditary  or  personal  ante- 
cedents, special  innate  characteristics,  and  idiosyncrasies  of  the 
individual ;  in  brief,  with  the  various  causes  to  which  we  have  con- 
stantly referred  to  explain  the  development  and  course  of  diseases. 

Differences  in  reaction  likewise  explain  differences  in  termination. 
When  reaction  is  energetic  and  timely  it  succeeds  in  destroying  the 
invading  microbes.  If  slight  and  slow  it  only  arrests  their  progress, 
and  the  process  passes  into  a  chronic  condition.  If  too  weak  or 
too  tardy  it  fails  to  save  the  organism,  and  the  disease  terminates 
in  death. 

These  considerations  suffice  to  demonstrate  that  the  same  in- 
fectious disease  may  present  varied  symptoms  and  follow  an  ex- 
tremely variable  evolution.  Supposing  all  conditions  to  be  the 
same  as  far  as  the  microbe  is  concerned,  the  influence  of  the  organism 
makes  itself  constantly  felt  and  contributes  to  modify  the  scene- 
Therefore,  a  certain  number  of  clinical  forms  have  been  admitted. 
These  divisions  are  evidently  arbitrary.     In  order  to  establish  them, 


EVOLUTION  OF  INFEOTIOUB  DI8EA8ES.  :,\'> 

the  various  cases  encountered  have  been  compared  with  an  habitual 
average  type,  running  its  course  without  the  intervention  of  any 
unusual  influence.  In  this  way  clinical  form  have  been  grouped 
under  two  heads:  First,  according  a  modifications  depend  upon 
some  anomaly  in  the  course,  morbid  symptoms,  or  localization. 
Second,  according  as  they  are  due  to  the  condition  of  the  subject. 
Willi  some  variation  this  division  may  be  applied  to  ;ill  infections. 

In  order  to  fix  the  ideas,  lei  us  consider  the  two  disea  e  in  which 
clinical  types  are  the  mosl  numerous  and  the  mosl  varied,  namely, 
pneumonia  and  typhoid  fever. 

The  following  two  tables  will  show  how  clinical  forms  may  be 
classified.  The  terms  sanctioned  by  usage  are  sufficiently  clem-  to 
make  description  unnecessary: 

CLINIC  \l,   li  )I!MS  <  >l     PNE1  m  IN]  \ 

I.  Divisions  Based  on  the  Study  of  the  Disease. 

1.  According  to  the  course. 
Abortive  pneumonia. 
Speedily  fatal   pneumonia. 
Prolonged  pneumonia. 

Double. 

With  successive  foci. 
Migrating. 
Infecting  pneumonia. 

2.  According  to  the  morbid  elements  or  symptoms. 
1  nflammatory  pneumonia. 

Adynamic  pneumonia. 
Ataxic  pneumonia. 
Pneumonia  with  icterus. 
Bilious  pneumonia. 

3.  According  to  localization. 
Pneumonia  of  the  base. 
Pneumonia  of  the  apex. 
Central  pneumonia. 
Massive  pneumonia. 
Pleuropneumonia . 

II.  Division  Based  on  the  Condition  of  the  Subject. 

1.  According  to  age. 
Pneumonia  of  children. 
Pneumonia  of  the  aged. 

2.  According  to  the  previous  state  of  health. 
Pneumonia  of  cachectics. 
Pneumonia  of  drinkers. 

Pneumonia  of  the  obese. 

Pneumonia  of  diabetics. 

Pneumonia  of  bronchiti.CS. 

Pneumonia  of  the  tubercular. 

Pneumonia  of  those  suffering  with~malaria.'etc. 


516  INFECT  10  US  DISEA  SES. 

3.  According  to  the  coexistence  of  another  injection. 
Pneumonia  of  typhoid  fever. 
Pneumonia  of  erysipelas. 

Pneumonia  of  acute  articular  rheumatism,  etc. 
Pneumonia  of  influenza. 

CLINICAL  FORMS  OF  TYPHOID  FEVER. 

I.  Divisions  Based  on  the  Study  of  the  Disease. 

1.  According  to  the  course. 
Abortive  typhoid  fever. 
Prolonged  typhoid  fever. 
Speedily  fatal  typhoid  fever. 
Typhoid  fever  with  relapses. 

2.  According  to  the  morbid  elements. 
Mucous  typhoid  fever. 
Ambulatory  typhoid  fever. 
Inflammatory  typhoid  fever. 
Bilious  typhoid  fever. 
Hemorrhagic  typhoid  fever. 
Ataxic  typhoid  fever. 
Adynamic  typhoid  fever. 
Putrid  typhoid  fever. 
Hyperpyretic  typhoid  fever. 
Sudoral  typhoid  fever. 

3.  According  to  the  localizations. 
Nervous  forms. 

Meningeal. 

Spinal. 
Thoracic  form. 
Gastric  form. 
Icteric  form. 
Renal  form. 
Cardiac  form. 
Septicemic  form. 

II.  Divisions  Based  upon  the  Condition  of  the  Subject. 

1.  According  to  the  age. 

Typhoid  fever  of  children. 
Typhoid  fever  of  the  aged. 

2.  According  to  the  previous  condition  of  health. 

Typhoid  fever  of  cachectics. 
Typhoid  fever  of  the  obese. 
Typhoid  fever  of  drinkers. 
Typhoid  fever  of  the  tubercular. 

3.  According  to  the  coexistence  of  another  infection. 

Typhoid  malaria. 

Laryngotyphus. 

Pneumotyphus. 

Termination  of  Infectious  Diseases. 

We  have  repeatedly  shown  that  the  organism  is  provided  with 
means  of  protection  which  prevent  penetration  and  multiplication 


EVOLUTION  OF  INFECTIOUS  DISEASES.  :,I7 

of  pathogenic  germs.  The  latter  may  succeed  in  invading  the 
economy  only  when  the  vigilance  of  the  cells  is  diverted  for  a  moment 
and  the  fluids  are  altered  by  some  affection.  The  di  ea  e  then 
manifests  itself.  Modifications  in  cellular  nutrition  are  immediately 
produced,  however,  which  transform  the  blood,  the  fluids,  and  the 
tissues,  and  make  of  them  unfavorable  culture  media  for  the  patho- 
genic agent.  Two  events  are  then  possible:  I.  In  Borne  case*  the 
changes  are  produced  slowly  and  progre  ively;  the  organism  gradu- 
ally rids  itself  of  the  germs  and  neutralizes  the  action  of  the  toxins 
which  impregnate  it.  Defervescence  is  -lowly  effected;  the  fever  u 
progressively  reduced  by  lysis,  and  the  various  functions  consume 
a  more  or  less  long  period  of  time  in  returning  to  their  normal  con- 
dition. M  is,  therefore,  possible  to  follow  the  progress  of  recovery 
day  after  day.  This  is  what  takes  place  in  typhoid  fever.  '2.  In 
other  instances,  on  the  contrary,  the  termination  is  abrupl  and 
sudden  as  in  pneumonia.     It  is  then  said  that  a  crisi  has  occurred. 

Crises.  From  the  earliest  antiquity  it  has  been  noted  thai  certain 
diseases  may  present  sudden  changes  in  their  evolution.  This  is 
crisis,  which  supervenes  when  the  corrupl  humor  (humeur  peccant) 
has  undergone  coction.  Nature  expels  it  from  the  body  or  causes 
its  deposition  in  some  part  of  the  economy.  The  latter  result  was 
formerly  considered  fortunate  or  unfortunate  according  as  deposition 
occurred  in  an  organ  of  little  importance  or  indispensable  to  life: 
These  ideas  led  Hippocrates  to  formulate  the  following  definition: 
"A  crisis  in  diseases  is  either  an  exacerbation,  decline,  a  metaptosris, 
another  affection,  or  the  end." 

The  crisis,  however,  did  not  occur  at  undetermined  periods.  It 
was  produced  on  fixed  days,  called  criticcd  days,  which  corresponded 
to  weeks  or  half  weeks — that  is  to  say.  to  the  fourth,  seventh,  tenth, 
fourteenth,  seventeenth,  and  twentieth  days.  The  critical  days 
were  preceded  by  the  indicating  days,  when  an  exacerbation  of  the 
symptoms  was  usually  observed.  We  must  add  that  Hippocrates 
did  not  regard  the  critical  days  as  possessing  an  absolute  value.  The 
crisis  might  occur  twenty-four  hours  sooner  or  later.  Galen,  on 
the  other  hand,  attributed  to  each  day  an  absolute  significance. 
He  contended  that  acute  diseases  did  not  last  more  than  forty  days, 
and  considered  the  crisis  as  a  sudden  reversion  to  health. 

The  latter  definition  has  prevailed.  At  the  present  day  the  name 
crisis  is  reserved  for  cases  in  which  the  change  is  favorable.  In 
infectious  diseases  this  change  is  characterised  by  the  following 


518  INFECTIOUS  DISEASES. 

phenomena:  A  sudden  fall  in  temperature,  a  rapid  increase  of  the 
urine,  the  re-establishment  of  secretions,  and  the  elimination  of 
noxious  substances  accumulated  during;  the  disease.  According  to 
prevailing  ideas  or  the  conceptions  of  the  observer,  attempts  have 
been  made  to'  define  crisis  by  thermal  defervescence  or  by  urinary 
modifications.  In  recent  years,  attention  having-  been  drawn  espe- 
cially to  the  modifications  of  cellular  activity,  Dr.  Chauffard  has 
proposed  the  following  definition:  An  intimate  and  sudden  act 
which  terminates  the  morbid  evolution  and  at  the  same  time  gives 
rise  to  an  ensemble  of  nutritive  and  functional  mutations. 

As  we  are  dealing  only  with  infections,  we  may  look  for  the  char- 
acteristic nature  of  the  crisis  in  the  most  striking  clinical  phenomena 
which  occur  at  this  moment  of  evolution.  The  symptomatic  modi- 
fication is  so  marked  as  to  have  sufficed  to  reveal  the  existence  of 
crises  before  the  introduction  of  the  modern  methods  of  investiga- 
tion, such  as  thermometry,  urology,  and  the  investigations  on 
nutrition. 

An  individual  who  was  deeply  infected  on  the  previous  evening 
is  found  completely  cured  on  the  following  morning.  This  is  the 
clinical  characteristic  of  the  crisis.  Setting  aside  all  theoretical 
discussions,  we  may  adopt  the  following  definition :  ' '  Crisis  is  char- 
acterized by  the  sudden  disappearance  of  morbid  manifestations." 
We  do  not  say  morbid  phenomena,  since  the  local  lesion  persists ;  it 
is  the  general  reactions  that  subside.  As  we  have  repeatedly  stated, 
these  reactions  are  dependent  upon  intoxication.  Consequently 
cessation  of  the  disturbances  indicates  that  the  poisons  have  been 
abruptly  eliminated  or  neutralized.  The  study  which  we  are  about 
to  undertake  will  show  that  the  latter  hypothesis  is  the  more  prob- 
able. On  the  ground  of  the  results  acquired  by  the  study  of  arti- 
ficial immunity  it  may  be  admitted  that  neutralization  of  the  poisons 
depends  upon  a  modification  in  the  cellular  nutrition  which  protects 
the  anatomical  elements  against  the  toxic  influence.  If  this  is  true 
we  ma3^  place  by  the  side  of  the  symptomatic  definition  above 
proposed  a  definition  drawn  from  the  very  essence  of  crisis — i.  e., 
from  the  study  of  pathological  physiology.  Therefore  we  may  say: 
"  Crisis  is  essentially  characterized  by  a  sudden  neutralization  of 
microbic  toxins,  namely,  by  an  immunity  conferred  upon  the  cells 
against  their  action."  To  those  who  may  wonder  why  this  terminal 
modification  is  produced  or  rather  manifested  in  a  sudden  manner 
we  shall  answer  that  the  situation  is  precisely  the  same  at  the  period 


EVOLUTION  OF  XNFE0TI0U8  DI8EA8E8.  519 

of  invasion.     For  instance,  pneumonia  begin    and  terminates  with 
the  same  instantaneousness. 

Supersaturation  of  the  organism  by  the  toxin  wa  nccfMaty  in 
order  for  a  reaction  to  be  produced  and  for  the  disease  to  be  estab- 
lished. Likewise,  supersaturation  of  the  organi  m  by  antitoxin*  i- 
necessary  in  order  for  the  disturbances  of  toxic  origin  to  be  neutral- 
ized. 

There  is  an  interesting  fad  thai  bad  nol  escaped  the  attention  of 
ancient  observers,  namely,  thai  crisis  is  oft  en  preceded  by  the  so-called 
precritical  phenomena,  consisting  in,  an  a1  times,  alarming  aggrava- 
tion of  the  symptoms.  The  temperature  rises  to  a  higher  figure 
than  on  the  preceding  days.  The  pulse  is  weaker  and  more  rapid. 
Dyspnea  is  very  intense,  and  sometimes  the  body  is  covered  with 
cold  perspiration.  The  subjective  sensations  experienced  l>y  the 
patient  are  in  harmony  with  these  objective  disturbances,  and 
hence  increase  the  anxiety  of  those  about  him.  The  contrasl  i- 
still  more  striking  when  the  individual  seems  to  be  cured  the  n<\\t 
morning. 

In  other  cases  the  crisis  is  preceded  by  a  procrisis.  The  temper- 
ature is  suddenly  reduced,  and  may  even  fall  to  the  normal.  The 
other  symptoms  subside,  and  one  migb!  believe  the  evolution  at  an 
end.  In  the  evening,  however,  the  disturbances  are  renewed,  to  be 
terminated  in  a  definite  manner  on  the  following  day.  In  still  other 
cases  a  false  crisis  occurs.  During  twenty-four  or  forty-eight  hours 
a  relative  subsidence  takes  place,  and  the  temperature  is  lower  than 
on  the  preceding  days.  Then  the  morbid  symptoms  are  again 
renewed  to  disappear  suddenly  and  definitively  a  few  days  later. 

In  most  cases  the  crisis  is  produced  during  the  night.  It  is. 
therefore,  surprising  to  see  the  patient  who  was  very  sick  the  previous 
evening  completely  cured  in  the  morning.  The  general  phenomena 
have  disappeared.  The  patient  realizes  this  by  the  feeling  of  well- 
being  which,  doubtless,  constitutes  one  of  the  most  astonishing 
manifestations.  He  has  the  feeling  that  the  disease  is  at  an  end  and 
that  he  has  entered  upon  convalescence.  The  tongue,  which  was 
dry,  becomes  moist.  The  skin,  which  was  dry  or  covered  with  cold 
perspiration,  recovers  its  agreeable  moisture.  The  pulse,  which  was 
weak  and  rapid,  becomes  strong  and  slow.  The  change  which  i>  at 
present  most  easily  observed  is  the  sudden  fall  of  temperature.  The 
patient  who  on  the  previous  day  had  104°  or  105.S°  F.  (40°  or  41°  C. 
has  no  more   than  98.6°  F.   (37°  C).     This  reduction  of  several 


520  INFECTIOUS  DISEASES. 

degrees  is  produced  within  twelve  hours.  In  some  cases,  however, 
it  is  effected  more  slowly — in  thirty-six  hours.  At  times  the  ther- 
mometer shows  a  fall  to  a  subnormal  degree,  not  exceeding  96.8°  F. 
(36°  C),  and  the  temperature  may  remain  at  this  point  for  several 
days. 

The  sudden  and  profound  change  produced  at  the  moment  of 
crisis  may  give  rise  to  new  nervous  reactions  which  constitute  the 
so-called  epicrisis.  In  children  this  is  manifested  by  convulsions; 
in  the  aged  by  collapse,  which  is  sometimes  so  marked  as  to  make 
it  a  difficult  matter  to  warm  the  patient.  In  adults,  delirium  and 
in  some  instances  delirium  tremens  occur.  I  have  observed  several 
cases  in  which  patients,  who  had  manifested  not  the  slightest  intel- 
lectual disorder  during  the  stationary  period,  develop  delirium, 
sometimes  of  an  intense  character,  at  the  moment  of  recovery, 
strangely  contrasting  with  the  amelioration  or  disappearance  of  the 
other  s}^mptoms.  The  intellectual  disturbance,  however,  is  rapidly 
cured,  and  does  not  indicate  an  unfavorable  prognosis.  Its  patho- 
genesis is  the  same  as  that  of  the  initial  delirium.  The  change 
suddenly  occurring  in  the  economy  has  disturbed  the  equilibrium 
or  the  quietude  of  the  predisposed  nervous  system,  thus  provoking- 
violent  reactions. 

Special  attention  must  be  devoted  to  changes  presented  by  the 
blood  and  the  secretions.  Dr.  Hayem  has  described  a  hemic  crisis, 
in  which  the  white  corpuscles,  increased  in  number  during  the 
disease,  resume  their  normal  number.  The  red  corpuscles  progres- 
sively diminish,  and  at  the  time  of  the  crisis  an  activity  on  the  part 
of  the  hematoblasts  occurs,  designed  to  increase  the  red  globules. 
We  have  already  referred  to  the  moisture  of  the  skin.  At  times 
this  cutaneous  manifestation  is  more  intense.  Sweating  is  profuse, 
and  serves  probably  for  elimination  of  the  toxins.  There  may  also 
be  observed  other  manifestations,  such  as  erythemata,  outbreaks 
of  urticaria  and  herpes,  sometimes  diarrhea,  a  bilious  attack,  or 
epistaxis. 

During  the  disease  the  quantity  of  urine  progressively  diminishes. 
At  the  moment  of  the  crisis  a  discharge  occurs.  The  polyuria  is  very 
abundant.  Voiding  of  two  and  three  litres  is  not  rare.  The  urine  is 
less  highly  colored  than  during  the  stationary  period.  At  this  time 
it  corresponds  to  the  numbers  4  and  5  of  the  scale  of  Neubauer  and 
Vogel.  At  the  time  of  defervescence  it  corresponds  to  the  numbers 
2  and  3.     Not  infrequently  the  density  is  increased.     In  one  instance 


EVOLUTION  OF  INFECTIOUS  DI8EA8E8.  521 

I  found  it  to  be  from  L. 025  to  L.031.  The  reaction  i  often  neutral 
and  sometimes  alkaline.  The  soluble  ubstance  undergo  till  more 
interesting  variations.  The  urea,  which  may  have  been  reduced  to 
12  or  L5  grams  during  the  stationary  period,  ri  e  to  30  or  K)  grams. 
The  chlorides,  which  were  represented  by  I  or  even  0.8  gram,  reach 
10  and  12  grams.  The  modifications  in  the  amount  of  chlorides 
have  been  attributed  fco  the  diet.  Thu  opinion  i  inadmif  ible,  for 
it  is  contradicted  by  the  abundant  discharge  at  the  momenl  of 
recovery.  II.  is  also  known  thai  if  chlorides  or  iodide*  are  admin- 
istered fco  pneumonia  patients,  these  substances  accumulate  in  the 
organism  and  are  eliminated  only  at  the  time  of  crisis.  Lifa 
the  phosphates  and  the  sulphates  increase  when  defervescence  \& 
established,  although  in  less  notable  proportions. 

The  same  is  true  with  regard  to  those  poisons  which  are  normally 
excreted  by  the  urine,  they  being  in  g^eal  pari  retained  in  the 
organism  during  the  disease.  During  the  stationary  period  the 
toxicity  of  the  urine  progressively  diminishes.  At  the  time  of  crisis 
it  is  considerably  increased  and  reaches  or  even  exceeds  the  normal 
figure.  It  should  not,  however,  be  concluded  from  this  resull  that 
recovery  is  due  to  the  sudden  elimination  or  to  the  urotoxic  discharge. 
On  the  contrary,  the  reverse  is  true.  Crisis  appears  because  tin- 
patient  has  recovered.  This  is  proved  by  the  fact  that  in  certain 
cases  the  urinary  crisis  occurs  twenty-four  hours  before,  or,  what  i- 
more  demonstrative,  after  recovery.  Thus,  the  patient  being  cured. 
he  is  capable  of  rejecting  the  poisons  which  impregnate  his  organism, 
but  to  which  he  had  already  become  insensible. 

Crisis  in  Pneumonia.  The  disease  in  which  crisis  i-  best  char- 
acterized is  incontestably  lobar  pneumonia.  In  typical  forms  the 
temperature  falls  to  the  normal  within  a  night. 

Pneumonia  does  not  always  terminate  in  this  manner,  however. 
This  infection  is,  perhaps,  the  one  in  which  the  symptoms  and 
evolution  are  most  modified  within  the  last  years.  Thus,  we  quite 
often  see  the  termination  effected  in  a  slow  and  progressive  manner. 
The  fever  is  reduced  little  by  little,  then  it  persists  for  day-  and  even 
weeks.  Under  such  conditions  diagnosis  becomes  difficult  and 
wavers  between  a  pneumonia  with  a  slow  course  and  a  pulmonary 
tuberculosis.  Even  in  such  cases,  however,  certain  critical  manifes- 
tations are  found,  especially  some  interesting  modifications  in  the 
characters  of  the  urine. 

Let  us  first  consider  the  observations  in  which  the  crisis  is  quite 


522  INFECTIOUS  DISEASES. 

clear.  In  such  cases  the  quantity  of  the  urine  is  increased,  but 
this  phenomenon  does  not  always  coincide  with  defervescence.  It 
may  begin  a  day  or  two  earlier  or,  on  the  contrary,  appear  only 
at  a  later  period.  At  times  the  polyuria  is  not  established  until 
the  moment  pf  convalescence.  The  amount  of  urea  is  sometimes 
increased,  at  other  times  diminished,  while  the  chlorides  are  always 
increased.  Furthermore,  we  have  pursued,  with  Dr.  Gaume,  some 
researches  on  the  variations  of  the  urinary  toxicity,  studying  from 
the  standpoint  of  the  urinary  syndrome  eleven  patients  suffering 
from  pneumonia.  In  seven  of  the  cases  the  termination  was  effected 
by  sudden  defervescence.  In  two  others  the  fever  terminated 
slowly  after  having  presented  numerous  variations.  In  the  last  two 
cases  the  disease  ended  fatally.1 

In  the  first  seven  cases  polyuria  was  present  only  twice.  The 
increase  of  the  urea,  however,  was  very  marked.  From  13  grams, 
which  was  the  figure  obtained  during  the  stationary  period,  the 
amount  of  urea  rose  suddenly  to  35  and  40  grams  and  even  50  grams. 
This  excess  was  observed  on  the  day  of  the  crisis  and  the  day  follow- 
ing. The  modifications  in  the  chlorides  were  still  more  striking. 
During  the  stationary  period  we  found  0.8  to  2  grams.  On  the  day 
following  defervescence  the  figure  rose  to  10  and  12  grams.  During 
the  disease  there  was  a  notable  diminution  in  the  urinary  toxicity, 
it  being  two  or  three  times  less  than  under  normal  conditions. 
This  result  may  be  partly  attributed  to  the  fact  that  the  patient 
was  confined  to  a  milk  diet;  but  this  condition  is  not  sufficient,  for 
it  cannot  explain  the  increase  of  toxicity  at  the  moment  of  the 
crisis,  when  the  diet  was  exactly  the  same  as  before.  I  believe, 
therefore,  that  the  various  urinary  poisons,  like  the  chlorides,  are 
retained  in  the  organism  and  are  eliminated  at  the  moment  of  the 
defervescence.  A  urotoxic  discharge  is  thus  produced,  lasting  for 
a  day  or  two. 

Thus,  urinary  toxicity  is  very  low  during  the  febrile  period  of 
pneumonia,  and  it  often  diminishes  as  the  disease  advances;  then 
a  urotoxic  discharge  suddenly  supervenes,  lasting  from  twenty-four 
to  forty -eight  hours,  and  reaching  its  maximum  on  the  day  of  thermal 
crisis,  exceptionally  on  the  following  day.  After  the  crisis  this 
toxicity  slowly  diminishes  in  some  cases,  rapidly  in  others,  and  may 
again  fall  to  extremely  low  figures  during  convalescence. 

1  Roger  and  Gaume.  Toxicity  de  Purine  dans  la  pneumonie.  Revue  de  midecine, 
April  10,  1889. 


/<;  v<>  L  UTIO  v  OF  I NFEOTIO  US  i>  I8EA  8E8. 

In  two  of  our  cases  the  fever,  instead  of  terminating  in  a  sudden 
manner,  was  reduced  slowly.  In  one  of  them  the  urotoxic  crisi 
was  produced  at  the  tnomenl  when  the  temperature  had  begun  to 
decline,  and  lasted  two  days,  presenting  the  usual  character  ,  in 
the  oilier  case  an  incomplete  crisis  wb  fir  I  observed,  coinciding 
with  a  urotoxic  crisis.  Subsequently  the  fever  recurred  and  the 
urinary  toxicity  ;ig;iin  diminished.  A  new  urotoxic  dischargi 
little  less  pronounced  than  the  first,  occurred  three  daye  later. 
From  this  momenl  on  the  course  of  the  disease  tended  rapidly 
toward  recovery. 

Finally,  in  two  of  the  cases  the  disease  terminated  in  death,  but 
the  evolution  was  in  several  respects  comparable  to  the  preceding 
two  cases.  The  course  was  prolonged.  There  was  do  defervescence, 
but  several  febrile  subsidences  occurred,  coinciding  with  urotoxic 
discharges. 

All  these  facts  concur  to  demonstrate  the  existence  of  a  urotoxic 
crisis,  even  in  fatal  cases,  although  in  the  latter  the  discharge  of  the 
poisons  is  not  well  marked. 

It  would  evidently  be  very  interesting  to  further  study  these 
phenomena  and  to  determine  the  substances  to  which  the  toxicity 
of  the  urine  is  due.  Feltz  and  Ehrmann  attribute  it  to  potassium 
salts,  but  the  analyses  which  we  have  made  have  not  enabled  us  to 
find  any  clear  relation  between  the  variation  of  the  salts  and  the 
changes  of  the  toxicity.  Authorities  are  at  present  inclined  to 
believe  that  a  toxic  role  is  played  by  ptomains,  produced,  perhaps, 
by  the  microbe  of  pneumonia.  Drs.  Lepine  and  Guerin  have  found 
alkaloids  in  pneumonic  urines.  By  examining  200  cubic  centi- 
metres of  urine,  they  found  ptomains  which  when  injected  into 
frogs  killed  them  within  twenty-four  or  forty-eight  hours.  In 
grave  cases  they  found  much  more  toxic  alkaloids.  Thus,  in  one 
observation  the  alkaloids  of  250  cubic  centimetres  of  urine  sufficed 
to  kill  a  frog  in  two  hours.  The  most  interesting  fact,  however,  is 
that  the  day  following  defervescence  they  could  obtain  hardly  any 
toxic  bases,  even  by  employing  900  cubic  centimetres  of  urine. 
Whatever  the  active  substances  may  be.  the  urine  oi  pneumonia 
patients  differs  from  normal  urine  in  that  it  is  highly  convulsant 
and  often  causes  salivation.  Normal  urine  also  contains  a  sial  2 
substance,  but  the  action  of  the  latter  is  masked  by  the  other  pois 
It  must  be  extracted  from  the  urine,  while  its  presence  is  manifest 
in  pneumonic  urine  even  when  the  total  urine  is  injected. 


524  IXFECTIO  US  D1SEA SES. 

Crisis  in  Typhus.  Next  to  pneumonia,  typhus  fever  is,  perhaps 
the  disease  which  most  clearly  terminates  by  crisis.  Its  fever  chart 
recalls  fairly  well  that  of  pneumonia.  The  rise  is  sudden,  and  on 
the  evening  of  the  first  day  the  temperature  reaches  102.2°  F- 
(39°  C).  During  the  stationary  period  the  fever  oscillates  between 
102.2°  and  105.8°  F.  (39°  and  41°  C).  Defervescence  is  often  pre- 
ceded by  a  precritical  period  during  which  the  temperature  is  slightly 
reduced.  At  the  moment  of  crisis,  which  is  effected  in  twenty-four 
or  forty-eight  hours,  it  often  falls  below  normal.  Coinciding  with 
the  fall  of  the  temperature  there  is  a  complete  and  truly  astonishing 
modification  in  the  general  condition  of  the  patient — stupor  dis- 
appears, the  skin  becomes  moist,  and  the  sleep  sound.  Finally,  the 
urine,  which  was  scanty  and  red,  becomes  profuse  and  pale. 

Crisis  in  Erysipelas.  Erysipelas  is  often  cited  among  diseases 
which  terminate  by  crisis.  In  fact,  there  are  cases  in  which  defer- 
vescence occurs  in  an  abrupt  manner  as  in  pneumonia,  Between 
evening  and  morning  the  temperature  falls  from  104°  to  98.6°  F. 
(from  40°  to  37°  C),  not  to  rise  again.  Oftener,  however,  defer- 
vescence takes  forty-eight  hours,  either  because  the  temperature  is 
reduced  gradually,  or  because,  after  a  fall  to  98.6°  F.  (37°  C),  it 
once  more  rises  on  the  evening  of  the  first  day,  and  does  not  remain 
normal  until  after  the  second  day.  Finally,  the  temperature  is  not 
infrequently  reduced  by  lysis,  presenting  a  series  of  variations. 
Whatever  the  mode  of  termination  may  be,  a  hypothermic  state  in 
which  the  temperature  falls  to  96.8°  F.  (36°  C),  sometimes  even 
to  96.4°  F.  (35°  C),  often  occurs  after  defervescence.  In  two  cases 
we  have  found  94.7°  F.  (34.8°  C.)  in  the  absence  of  any  notable 
disturbance. 

The  study  of  thermal  modifications  should  be  supplemented  by 
investigation  of  the  urinary  variations.  The  researches  which  we 
have  pursued  on  this  subject,  with  the  assistance  of  Dr.  Marsat,1 
demonstrated  that  the  modifications  are  analogous  to  those  observed 
in  pneumonia,  except  that  they  are  less  pronounced.  During  the 
stationary  period  the  urine  is  scanty.  The  amount  does  not  exceed 
700  or  900  cubic  centimetres,  the  color  being  mahogany  red.  The 
density  rises  and  varies  between  1.022  and  1.030.  The  reaction  is 
acid.  At  the  moment  of  convalescence  a  critical  polyuria  is  pro- 
duced.    The  amount  voided  rises  to  1500  and  2000  cubic  centi- 

1  Marsat,     Essai  d'urologie  olinique  dans  l'6rysipelc.     Thfese  de  Paris,  1S94. 


EVOLUTION  OF  INFECTIOUS  DISEASES.  525 

metres.  The  color  is  clearer,  and  the  density  fEll  bo  L.017and  L.010. 
At  this  time  a  transitory  incontinence  of  urine  which  la  I  a  da 
two  occasionally  occurs  in  women.  The  modification  in  the  urea, 
phosphates,  and  chlorides  are  far  less  marked  and  clear  than  in 
pneumonia.  The  chlorides  diminish,  as  in  pneumonia.  ('i  the  • 
from  2  to  o'  grams  are,  however,  found  during  the  Btal  ionary  period. 
At  the  moment  of  convalescence  the  daily  figure  rises  to  I-  and  13 
grams.  The  modifications  in  the  phosphates  are  very  irregular. 
In  the  majority  of  cases  (here  is  diminution  during  thi  tationary 
period  and  n  return  i,o  (he  normal  al  the  time  of  convalescence ;  but 
the  modifications  in  the  phosphates  are  often  produced  iii  a  -udden 
and  unexpected  way  which  is  not  explained. 

Crisis  in  Scarlatina.  Among  the  eruptive  fevers  scarlatina  de- 
serves particular  attention.  The  researches  pursued  in  our  labor- 
atory by  Dr.  Mazaud1  showed  with  accuracy  the  urotoxic  variations 
produced  in  this  infection.  At  the  beginning  of  scarlatina  the  urine 
is  scanty.  The  absolute  toxicity  is  high  —  i.  <■.  a  small  amount 
when  injected  into  animals  suffices  to  cause  death.  If,  however, 
the  volume  is  taken  into  account,  it  is  found  that  the  individual 
eliminates  in  the  twenty-four  hours  less  poison  than  under  normal 
conditions.  When  the  urine  is  albuminous  it  often  presents  peculiar 
properties.  It  gives  rise  to  intestinal  movements  which  are  more 
or  less  violent  and  followed  by  diarrhea.  These  manifestations  are 
absent  when  the  urine  contains  no  albumin.  It  is,  therefore,  prob- 
able that  the  albumins  of  the  stationary  period,  which  are  mainly 
constituted  by  globulins,  possess  toxic  properties.  Whether  albu- 
minous or  not,  the  urine  at  the  beginning  of  the  disease  is  always 
convulsant.  Hence  it  seems  to  contain  nerve  poisons,  a  fact  which 
is  in  perfect  harmony  with  the  symptoms  presented  by  the  patients. 

At  the  moment  of  recovery  a  urinary  crisis  occurs,  supervening 
in  most  cases  on  the  tenth  or  eleventh  day.  The  urinary  and  the 
urotoxic  crisis  are  effected  at  about  the  same  time,  but  the  coinci- 
dence is  not  absolute.  An  interesting  fact  is  that  the  temperature 
is  always  reduced  before  the  urotoxic  crisis  appears.  In  scarlatina 
as  well  as  in  pneumonia  recovery  precedes  and  explains  the  crisis. 

Crises  in  Various  Infections.  Among  the  other  infections  Termin- 
ating by  crisis,  although  less  marked  and  clear  than  in  the  preceding 
examples,  variola,  varioloid,  and  mumps  may  be  cited,  as  well  as 

1  Mazaud.  Recherches  experiment  ales  sur  les  variations  de  la  texicite  des  urines  au 
cours  de  la  scarletine.     These  de  Paris.  1S98. 


526  INFECTIOUS  DISEASES. 

typhoid  fever,  which  in  one-fourth  of  the  cases,  according  to  Prof. 
Jaccoud,  instead  of  terminating  slowly,  as  is  the  rule,  ends  abruptly. 
We  may  likewise  mention  malaria,  the  crises  of  which  have  been 
well  studied  by  Mosse",  Roques,  and  Lemoine;  and  recurrent  fever, 
the  spirilla  of  which  appears  in  the  blood  before  the  paroxysm  and 
disappear  a  little  before  the  crisis.  Infectious  icterus  must  not  be 
overlooked.  Chauffard  has  thoroughly  studied  the  characters  of  the 
urinary  crisis  in  catarrhal  icterus.  Since  the  works  of  Bouchard 
and  of  Mosse  it  is  known  that  primary  grave  icterus  often  terminates 
in  recovery  and  that  disappearance  of  the  symptoms  coincides  with 
a  urinary  crisis  running  a  course  parallel  to  the  increase  in  the  urine 
and  urea.  Another  element  may  at  present  be  added — i.  e.,  urinary 
toxicity. 

Cholera.  There  is  a  disease  in  which  crisis  occurs  in  a  reverse 
direction:  that  is  cholera.  In  the  stationary  period  the  temperature 
is  below  normal.  At  the  moment  of  recovery  it  rises  above  and 
sometimes  reaches  a  figure  notably  above  the  normal.  Thus  a 
febrile,  reactionary  period  develops,  sometimes  attended  by  grave 
manifestations  which  may  impart  to  the  patient  a  typhoid  aspect. 

Conclusions.  The  facts  above  reported  suffice  to  demonstrate 
that  crisis  is  the  result  and  not  the  cause  of  recovery.  It  must  be 
considered  simply  as  a  process  resulting  from  an  exaggeration  of 
normal  phenomena.  It  is  established  that  in  a  healthy  man  the 
elimination  of  autogenous  poisons  is  not  effected  in  a  continuous 
manner.  The  urinary  secretion  varies  from  one  day  to  another. 
It  follows  a  tertian  and  less  frequentty  a  quartan  type.  Then,  even 
in  a  normal  state  of  things,  accumulations  and  discharges  are  con- 
stantly produced — that  is  to  say,  little  crises.  This  is  a  particular 
example  of  a  general  law.  We  have  already  shown  that  there  is 
no  uniform  movement  in  nature,  and  that  all  vital  acts  are  remittent. 
Starting  from  this  physiological  fact,  we  may  regard  crisis  as  a 
natural  phenomenon  or  an  exaggeration  of  the  normal  type. 

On  the  other  hand,  it  seems  to  us  that  the  termination  of  the 
disease  must  be  attributed  to  a  change  occurring  in  the  activity  of 
the  infectious  agent.  Netter  and  Patella  have  shown  that  at  the 
moment  of  crisis  the  pneumococci  succumb  or  are  attenuated.  It 
is  probable  that,  under  the  influence  of  antitoxins,  the  microbe 
ceases  to  elaborate  toxins.  At  the  same  time  the  cellular  reaction 
which  has  terminated  in  the  production  of  antitoxins  must  have 
armed  the  nervous   centres  against  the  effects  of  impregnation. 


EVOLUTION  OF  INFECTIOUS  DISEASES,  527 

When   this  reactionary  process  is  a1  an  end    the  nervoi 
become  indifferenl  to  the  toxins  which    'ill  remain  in  the  economy, 
and  which,  as  experience  demon  are  nol  eliminated  until 

twenty-four  hours  later.      Hence  we  conclude  thai    the  prin 
phenomenon  is  a  chemical  tram  formation  occurring  in  the  organism 
protecting  the  cells  againsl   the  toxins;  in  other  word  .  rendering 
the  cells  capable  of  enduring  the  microbic  poison  as  if  the  organism 
were  vaccinate) I.     Under  these  conditions  the  toxic  action  i 
longer  exercised.    The  symptoms   disappear,   cellular  activil 
re-established,  and  elimination  of  the  poisons  may  I"-  effected.    This 
is  the  last  act  of  the  critical  evolution. 

Convalescence.  When  the  morbid  process  3eems  to  have  been 
arrested  and  recovery  established,  the  organism  fc  qoI  yel  com- 
pletely restored  to  its  normal  condition.  There  is  -till  a  lasl  period, 
termed  convalescence. 

The  appetite,  which  had  been  suppressed  during  the  diw 
reappears,  and  ii  is  often  so  marked  thai  it  is  difficull  to  prevenl  th<- 
patient  from  overeating.  The  temperature  often  falls  below  normal. 
The  figures  07.7°  and  96.8°  F.  (36.5°  and  36°  C.)  are  nol  infrequent, 
and  may  be  observed  for  a  week  or  more.  Emaciation  appears  or 
increases,  this  probably  being  due  to  the  greal  amounl  of  \ 
which  is  eliminated  by  the  different  emunctories,  notably  through 
the  respiratory  apparatus  and  the  kidney.-.  Then,  at  the  end  of  a 
few  days,  the  patient  grows  fat,  his  weight  often  exceeding  that 
noted  before  the  commencement  of  the  disease,  and  at  times  he 
becomes  slightly  obese.  The  nervous  system  having  been  most 
affected  during  the  stationary  period,  therefore  returns  more  slowly 
to  its  normal  condition.  During  the  first  days  following  recovery, 
when  all  the  organs  are  working  regularly,  the  nerv<  m  is 

still  disturbed.  The  individual  is  unable  to  keep  on  his  feet  or  walk. 
If  an  abrupt  movement  is  attempted,  dizziness  and  palpitation  are 
experienced.  Now  and  then  a  febrile  paroxysm  occurs,  as,  for 
instance,  when  he  happens  to  read  a  little  too  much,  or  on  the 
occasion  of  a  visit,  an  emotion,  or  an  exertion  of  little  importance, 
such  as  making  his  toilet.  The  thermometer  then  marks  LOO. 
101.3°  F.  (38°  or  38.5°  C).  These  disturbances,  which  seem  to 
depend  simply  upon  a  lack  oi  equilibrium  in  the  centres  of  thermal 
regulation,  and  not  upon  an  additional  infection,  are  transitory  anil 
in  no  wise  disquieting.  The  nervous  manifestations  of  convales- 
cence, however,  are  sometimes  much  more  marked  than  would  be 


528  INFECTIOUS  DISEASES. 

expected  in  view  of  the  comparatively  innocent  character  of  the 
disease.  In  this  regard  nothing  is  more  instructive  than  influenza. 
Even  after  the  slight  forms  which  have  lasted  but  a  few  days,  con- 
valescence is  very  tedious.  Weakness,  asthenia,  and  incapacity  for 
work  may  persist  for  weeks  or  months.  Finally,  some  of  the  symp- 
toms of  the  stationary  period  may  reappear.  A  convalescent  from 
typhoid  fever  will  easily  have  diarrhea.  A  convalescent  from  a 
thoracic  affection  will,  upon  the  slightest  cause,  cough  and  have  pain 
in  the  side. 

Evidently,  the  duration  of  convalescence  varies  according  to  the 
nature,  type,  and  gravity  of  the  disease,  and  also  according  to  the 
age  or  previous  condition  of  the  subject.  Aged  individuals  and 
those  who  are  already  weakened  require  more  time  to  be  re-estab- 
lished, and  it  may  often  be  necessary  for  them  to  go  to  the  country 
or  to  a  warm  climate. 

Convalescence  may  be  interrupted  by  a  variety  of  accidents. 
Besides  the  nervous  fevers  already  referred  to,  other  causes  may 
produce  a  rise  of  temperature  up  to  102.2°  or  104°  F.  (39°  or  40°  C). 
After  a  (\&y  or  two  the  temperature  again  becomes  normal.  This 
is  often  a  process  of  abortive  relapse.  The  disease,  not  being  well 
extinguished,  recommences  and  is  arrested  by  means  of  timely 
medication  or  the  natural  defenses  of  the  organism.  In  other 
instances  a  septicemia  is  superadded  to  the  primary  disease.  Some 
authorities  have  even  maintained  that  the  relapses  of  typhoid  fever 
should  be  considered  as  infections  of  intestinal  origin — i.  e.,  that  the 
alterations  of  Peyer's  patches,  by  lessening  the  means  of  defense, 
permit  the  invasion  of  the  economy  by  the  habitual  microbes  of  the 
alimentary  canal. 

Febrile  paroxysms  connected  with  cutaneous  suppurations  may 
also  be  observed.  The  alterations  of  the  skin,  like  those  just  referred 
to  in  the  intestine,  permit  the  pus  cocci  to  produce  abscesses  or  boils. 
At  times  an  infection  is  produced  in  other  organs.  For  example, 
pneumonia  may  be  observed  during  convalescence  from  any  disease. 
Lastly,  in  certain  cases  febrile  paroxysms  occur,  which  are  ex- 
plained by  the  aggravation  of  an  antecedent  chronic  infection.  For 
example,  in  an  individual  who  has  suffered  for  a  more  or  less  con- 
siderable period  with  a  torpid  or  slow  tuberculosis,  and  then  con- 
tracts measles,  convalescence  does  not  become  duly  established  after 
this  intercurrent  infection.  He  remains  weak  and  suffering.  He 
has  slight  fever  every  night.     The  symptoms   may  thus  evolve 


EVOLUTION  OF  INFECTIOUS  DISEASES. 

rapidly  LowmkI  ;i.  f"«- i,i  .* 1 1  termination,  or,  on  the  contrary,  they 
after  a  certain  time  be  arrested  and  disappear, 

Relapses  and  Recurrences.  Convalescence  may  also  be  inter- 
rupted by  a  relapse.  In  fact,  in  certain  infections  relapse  is  the 
rule  Such  is  the  case  in  recurrent  fevert  and  a  particular  form  of 
infectious  icterus,  improperly  called  Weil's  di  ea  e. 

Relapse  is  particularly  frequenl  in  typhoid  fever,  influenza,  and 
bronchopneumonia.  It  is  rare  in  lobar  pneumonia,  and  exceptional 
in  other  infections.  Not  infrequently  il  is  caused  by  a  fault  of  the 
physician  or  of  the  patient.  Alimentation  may  have  been  too  rapid 
or  too  abundant;  the  patient  may  have  :s<>\  up  too  soon,  or  expo  ed 
himself  to  cold,  and  especially  to  fatigue.  It  is  relatively  easy  to 
treat  a  disease  during  the  stationary  period,  but  at  the  momenl  of 
convalescence  the  physician  is  often  greatly  embarrassed  and  requires 
much  tact  and  experience. 

Relapse  sometimes  manifests  itself  in  a  slow  and  progressive 
manner.  More  often  it  appears  suddenly,  even  in  the  case  of  I  v|  >hoid 
fever.  In  this  disease  the  temperature  reaches  102.2°  or  104°  F. 
(39°  or  40°  C.)  on  the  evening  of  the  first  day.  In  a  general  way, 
relapses  are  less  grave  and  of  shorter  duration  than  the  primary 
affection.  There  are  many  exceptions  to  this  rule,  however,  and  a 
relapse  may  be  more  prolonged,  graver,  and  even  fatal. 

In  scarlatina  we  have  never  observed  true  relapses.  We  have 
observed  erythemata  of  convalescence,  which  we  have  already  re- 
ferred to,  and  which  coexist  with  various  infectious  manifestations,  a 
knowledge  of  which  singularly  elucidates  the  significance.  Such  is 
not  the  case  with  measles.  At  times  a  child  presents  a  slight  erup- 
tion attended  with  slight  fever  and  diarrhea.  Measles  is  diag- 
nosed, the  symptoms  resolve,  and  a  few  days  later  an  eruption, 
likewise  accompanied  by  catarrh  and  fever,  makes  its  appearance. 
This  second  attack  is  generally  more  intense  and  better  characterized 
than  the  first.  In  one  case  in  which  the  contagion  was  clearly 
established  the  first  attack  occurred  on  the  seventh  day.  and  the 
second  renewal  in  due  time,  namely,  on  the  twelfth  day.  The  first 
manifestation  may,  therefore,  be  considered  as  a  sort  of  rubeoliform 
rash;  for  it  seems  logical  to  admit  that  the  eruption  occurring  at 
the  habitual  moment  is  the  true  one. 

Variola  is  not  a  disease  in  which  relapses  are  observed.  It  must 
be  noted,  however,  that  in  certain  instances  some  new  pustules 
may  appear  toward  the  twentieth  day,  especially  upon  the   soles 

34 


530  IXFECTIO  US  DISEASES. 

of  the  feet.     At  all  events,  they  are  not  numerous,  and  rapidly 
disappear. 

Relapses  have  often  been  observed  in  diphtheria.  Here  is  a  fine 
example:  The  patient  had  been  treated  by  serumtherapy.  His 
angina,  which  was  of  a  quite  serious  character,  was  on  the  way  to 
recovery,  when  one  morning  he  found  the  throat  again  covered 
with  pseudomembranes  containing  a  large  number  of  Loeffler's 
bacilli.  Although  this  patient  had  already  received  60  c.c.  of 
serum,  we  gave  two  new  injections  of  30  c.c.  each.  The  false 
membranes  were  detached  in  four  days,  but  the  patient  died  from 
diphtheritic  paralysis. 

Recurrences.  A  distinction  has  justly  been  established  between 
relapse  and  recurrence.  Relapse  means  a  new  beginning  of  a  disease 
without  a  new  infection.  Recurrence  is  connected  with  a  new 
infection.  In  a  good  manj'-  cases  the  distinction  is  easy.  When  a 
person  is  attacked  with  typhoid  fever  or  erysipelas  after  an  interval 
of  fifteen  or  twenty  years,  such  is  evidently  a  case  of  recurrence. 
When,  however,  the  symptoms  reappear  at  an  early  period,  inter- 
pretation becomes  extremety  difficult.  Some  individuals,  particularly 
women,  have  erysipelas  everj^  month.  Is  such  a  case  an  example 
of  recurrence  or  of  a  relapse?  It  is  impossible  to  answer,  since  we  do 
not  know  what  period  of  time  is  required  for  the  destruction  of  the 
germ. 

The  present  tendency  is  to  increase  the  importance  of  relapses  at 
the  expense  of  recurrences,  and  to  admit  that  the  microbes  remain 
inactive  in  the  organs  and  tissues,  but  ever  ready  to  assume  the 
offensive  upon  the  slightest  occasional  cause.  Indeed,  it  has  even 
been  asserted  that  in  most  cases  the  recurrences  of  gonorrhea  are  but 
relapses.  In  fact,  the  gonococcus  persists  during  an  almost  indefinite 
period  of  time  in  the  urethra  which  it  has  once  invaded.  Erysipelas 
and  pneumonia  are  among  the  diseases  which  seem  truly  capable  of 
frequent  recurrences.  Recurrences  of  measles  are  quite  common; 
those  of  typhoid  fever,  smallpox,  and  scarlatina  are  very  rare. 
According  to  the  information  furnished  by  our  patients,  recurrences 
of  measles  are  observed  in  14  per  cent,  of  the  cases  in  adults;  that 
of  scarlatina  is  encountered  once  in  a  hundred  cases.  As  to  syphilis, 
recurrence  is  altogether  exceptional.  Most  of  the  cases  cited  as 
examples  of  second  chancre  are  accounted  for  by  a  confusion  with 
tertiary  lesions  of  the  genitals,  which  sometimes  simulate  a  primary 
lesion. 


EVOLUTION  OF  INFECTIOUS  DI8EA8E8.  :,.;l 

Passage  of  Acute  Infections  to  a  Chronic  Condition.     Although 
recovery  is  the  normal  termination  of  infectiou    di  ea  e  .  there  are 
certain  cases  in  which  the  evolution  i    prolonged  beyond  the  u 
limits.    The  disease  is  then  said  to  have  become  chronic. 

The  duration  of  acute  diseases  Ins  been  arbitrarily  fixed  al  forty 
days.  Beyond  this  term  chronicity  is  uppo  ed  to  be  e  tablished. 
If  the  question  be  considered  from  a  higher  standpoint  it  will  be 
recognized  that  an  essential  difference  between  the  two  proc< 
is  furnished  by  the  study  of  the  evolution.  Acute  disease  i-  a 
morbid  process  in  a  state  of  continuous  modification.  Each  day 
brings  about  a  change  which,  though  often  but  slightly  marked,  can 
nevertheless  be  recognized  by  a  careful  examination.  It  will  then 
be  noted  that  the  organism  is  reacting— thai  is,  struggling  with  all 
its  forces  to  arrest  and  destroy  the  morbific  cause;  it  is  in  revolt 
against  the  invader.  In  a  chronic  disease  the  organism  submits  to 
the  yoke  of  the  pathogenic  agent,  and  seems  to  have  no  other  ambi- 
tion than  to  live  with  it.  It  hardly  tries  to  circumscribe  its  progress. 
It  abandons  itself,  being  incapable  of  continuing  the  battle.  The 
reason  the  condition  of  the  patient  is  not  more  quickly  reduced 
is  that  the  invader  itself  has  become  less  active  and  aggressive.  In 
this  manner  a  tacit  agreement,  as  it  were,  is  made  between  the 
microbe  and  the  organism,  and  the  disease  persists,  undergoing  only 
extremely  slow  changes. 

Therefore,  an  acute  disease  is  distinguished  by  a  lively  and  not 
infrequently  by  a  too  energetic  reaction.  A  chronic  disease  is 
characterized  by  the  absence,  inefficiency,  or  the  slowness  of  reac- 
tion. 

At  times,  however,  the  organism  may  for  a  moment  recover  its 
energy.  The  result  is  acute  attacks,  often  occurring  without  any 
appreciable  cause,  and  at  times  as  a  consequence  of  exposure  to 
cold,  traumatism,  or  an  intercurrent  infection.  Under  these  con- 
ditions the  pathogenic  microbe  makes  a  fresh  attack,  with  the  result 
that  the  organism  shakes  off  its  torpidity.  This  acute  spell  may 
be  illy  directed,  undisciplined,  and  precipitate  the  morbid  evolution, 
and  thus  rapidly  terminate  in  death.  In  other  instances,  after 
having  given  rise  to  painful  symptoms,  it  leads  the  organism  to 
recovery.  A  rebellious  gonorrhea,  for  example,  has  been  seen  to 
disappear  after  a  new  acute  attack. 

Medicine  has  attempted  to  imitate  these  natural  procedures. 
Irritant    local    applications    may   realize    this    indication.     Koch's 


532  INFECTIOUS  DISEASES. 

tuberculin  does  not  act  otherwise.  It  whips,  so  to  say,  the  torpid 
evolution  of  chronic  tuberculosis. 

An  acute  process  may  become  chronic  without  the  production  of 
any  notable  changes.  It  stops  at  a  given  moment  of  its  course. 
This  ma}'  occur  at  the  moment  of  aggravation  as  well  as  at  the  time 
of  improvement  of  the  disease.  The  violent  manifestations  subside, 
the  reactions  and  pains  cease,  and  in  certain  cases  the  symptoms  are 
so  slight  as  to  lead  the  patient  to  the  belief  that  he  is  cured.  Illus- 
trations abound.  They  are  drawn  mostly  from  cases  of  non-specific 
infections,  mainly  inflammations  of  organs — e.  g.,  enteritis,  nephritis, 
and  cystitis,  which  gradually  pass  into  a  chronic  condition;  also 
various  commonplace  or  specific  suppurations.  Gonorrheal  ure- 
thritis, for  instance,  is  thus  transformed,  and  often  persists  during 
.an  entire  lifetime,  occasioning  no  disturbance,  and  unknown  even 
to  the  patient.  Finally,  of  the  specific  infections,  we  must  especially 
mention  tuberculosis,  which,  after  an  acute  attack,  may  follow  a 
.slow  evolution. 

In  order  to  more  closely  study  the  evolution  of  chronic  lesions 
let  us  consider  an  abscess  somewhat  deeply  situated.  In  its  develop- 
ment it  produces  various  disturbances;  then,  when  it  is  opened 
to  the  exterior,  the  sjmrptoms  cease.  Suppuration,  which  is  at  first 
very  abundant,  diminishes  progressively.  An  early  recovery  may  be 
expected.  At  a  certain  moment,  however,  improvement  is  arrested, 
and  a  fistula  discharging  a  seropurulent  fluid  is  established.  There 
is  no  longer  any  general  or  local  reaction.  This  lesion,  which  be- 
comes chronic,  is  borne  by  the  organism  without  any  apparent 
inconvenience.  However,  at  the  moment  when  chronicity  is  estab- 
lished, the  discharge  undergoes  some  modifications.  It  loses  its 
freely  purulent  character;  it  becomes  more  serous  and  more  mucoid, 
and  at  the  same  time  the  microbes  diminish  in  number  and  virulence. 
Failure  to  recover  in  such  instances  is  often  due  to  the  presence  of  a 
foreign  body,  a  splinter,  or  a  sequestrum  in  the  focus;  or  else  there 
is  diseased  tissue  at  the  bottom  of  the  fistula.  When  it  is  possible 
to  intervene  and  extirpate  or  remove  this  inflammatory  body,  the 
organism  triumphs  over  the  bacteria  and  the  lesion  heals.  Thus 
foreign  bodies,  although  absolutely  harmless  when  they  are  aseptic, 
maintain  an  infection  which  would  be  cured  in  their  absence.  This 
is  a  remarkable  example  of  pathogenic  association. 

The  microbe,  although  attenuated,  is  not  absolutely  inoffensive 
in  such  chronic  conditions.     It  seems  even  that  its  feeble  pathogenic 


EVOLUTION  OF  fNFECTIOUS  DI8EA8E8. 

potency  depends  mainly  upon  some  protective  powi  d  by  the 

w;i,ll  of  the  morbid  focus.  Chauveau  ha  hown  thai  the  pu  ol  b 
no  ton  which  product's  no  di  turbance  i  virulent.  It  8  particle  "f 
it  be  inoculated  into  another  poinl  of  the  economy,  di  turbances 

are  produced.     The  pus  was  endured  only  in  itfl  old  foCU  , 

In  cases  of  chronic  suppuration  fistula  may  from  time  to  time 
become  occluded.    The  subjacenl  focus  i    then  filled  with  pue  and 
increases  in  volume;  h   becomes  painful  and  give    ri  e  to  f( 
After  an  artificial  or  natural  opening  the  lesion  re  nine    itc 
and  chronic  course.     In  oilier  instances  the  fistula  becomes  closed; 
it  appears  to  be  healed;  as  no  3ymptom  is  any  longer  apparent. 
For  months  or  years  the  lesion  gives  rise  to  no  disturbance  what* 
Mien  the  focus,  which  seemed  extinguished,  ie  again  kindled  and  a 
new  attack  is  produced.    Such  a  course  is  produced  especially  in 
cases  of  osteomyelitis,  where  a  sequestrum  may  give  rise  to  very 
tardy  disturbances  at  considerable  intervals.     The  microbe  slumbers 
for  years  as  an  absolutely  inoffensive  guest.     An  occasional,  often 
unnoticeable,  cause  enables  it  to  recover  a  certain  degree  of  viru- 
lence and  to  arouse  inflammatory  reactions. 

A  similar  evolution  is  sometimes  observed  after  typhoid  fever. 
This  disease  never  passes  into  a  chronic  state,  but  the  microbe  that 
causes  it  may  become  localized  at  certain  points,  notably  in  the 
bone-marrow,  and  thus  call  forth  a  slow  inflammation  which  termi- 
nates, after  several  months,  in  a  focus  of  osteomyelitis.  Bacterio- 
logical examination  demonstrates  the  presence  of  Eberth's  bacillus 
therein.  In  this  case  the  acute  disease  ends  in  a  chronic  pr< 
quite  different  from  what  it  had  originally  been. 

We  can  find  highly  interesting  illustrations  in  the  history  of  ul< 
Let  us  consider,  for  example,  the  varicose  ulcer.  A  slight  lesion,  an 
abscess,  a  pustule,  a  simple  abrasion  having  induced  an  infection 
so  mild  that  no  symptom  is  produced,  and  the  existence  of  which  we 
admit  simply  by  induction,  is  the  starting  point.  Reparation  is  not 
effected  because  the  tissues  were  altered.  Their  nutrition  was  pro- 
foundly disturbed  by  the  varicose  condition  of  the  vein-.  The  skin 
had  become  hard,  brownish,  and  sometimes  the  seat  of  eczema. 
Therefore,  the  little  lesion  sufficed  to  produce  a  chronic  affection  in 
the  suffering  tissue.  The  same  explanation  is  applicable  to  ulcer- 
ating dermosynovitis.  This  is  a  trophic  lesion  induced  by  an  ordi- 
nary cause  or  a  slight  infection,  and  it  develops  and  persists  because 
nutrition  is  profoundly  disturbed  by  nervous  lesions. 


534  /  -V I'ECTIO  US  DISEA  SES. 

Experimentation  confirms  the  data  of  clinical  observation  by 
demonstrating  that  section  of  sensory  nerves  hinders  considerably 
the  process  of  repair.  For  example,  division  of  the  sciatic  nerve 
in  a  guinea-pig  is  often  followed  by  ulcerations  in  the  foot  operated 
upon ;  but  if  care  be  taken  to  protect  the  limb  by  means  of  a  sort 
of  plaster  shoe,  infection  is  prevented,  and  no  nutritive  disturbance 
appears. 

The  same  is  true  of  ulcers  of  mucous  membranes.  A  common- 
1  dace  lesion,  in  most  cases  of  infectious  origin,  may  serve  as  a  starting 
point  for  an  ulcer  of  the  esophagus,  duodenum,  and  especially  of 
the  stomach.  Ulcer  of  the  stomach  develops  in  hyperchlorhydric 
dyspeptics.  The  excess  of  acid  hinders  reparation.  Filhene  has 
given  an  experimental  demonstration  of  this  pathogenesis:  Two 
rabbits  received  considerable  doses  of  arsenic  subcutaneously.  In 
one  of  them,  kept  as  a  control,  gastric  ulcers  developed ;  in  another, 
to  which  bicarbonate  of  soda  was  administered  to  neutralize  the 
gastric  juice,  no  lesion  was  produced. 

Although  the  organism  plays  a  very  important  part  in  the  develop- 
ment of  ulcers,  we  must  recognize  that  the  lesion  is  sometimes 
dependent  upon  the  nature  of  the  pathogenic  agent,  its  degree  of 
virulence,  and  the  point  at  which  it  is  developed.  The  ulcerations 
of  tuberculosis,  glanders,  and  syphilis  and  phagedenic  lesions  belong 
to  this  group.  The  influence  of  the  organism,  without  being  abso- 
lutely null,  is  in  such  cases  considerably  reduced. 

An  acute  lesion  may  pass  into  a  chronic  state  under  a  form  rela- 
tively favorable,  namely,  induration.  In  such  instances  the  organism 
succeeds  in  completely  destroying  the  pathogenic  agent,  but  the 
ulcerations  produced  are  too  profound  to  admit  of  perfect  reparation. 
The  tissue,  instead  of  returning  to  its  primary  condition,  is  replaced 
by  a  newly  formed  fibrous  production.  This  termination  is  observed 
in  superficial  lesions,  in  certain  abscesses,  and  in  adenopathies;  but 
it  is  particularly  important  in  deeply  situated  tissues  and  organs. 
In  this  manner  cicatrices  are  produced  which,  when  located  in  the 
mucous  membranes,  cause  deformity  and  embarrass  their  normal 
action.  When  located  in  such  passages  as  the  esophagus  or  the 
urethra  they  result  in  stricture;  in  the  viscera,  such  as  the  heart, 
liver,  or  kidneys,  they  produce  sclerosis.  In  these  cases  the  chronic 
process  differs  completely  from  the  acute.  As  we  have  shown  in 
treating  of  sclerosis,  the  process  of  repair  remedies  the  first  disturb- 
ances, but  creates  ahinderance  to  the  regular  activity  of  the  organs. 


EVOLUTION  OF  INFECTIOUS  DI8EA8E8. 

The  chronic  processes,  the  mechani  m  of  which  we  have  indicated 
above,  undergo  no  modification  or  evolve  lowly  eithei 
recovery  or  toward  death,  [nbothin  fcance  change  ending  in  one 
or  the  other  of  these  two  termination)  are  produced  either  in  an 
insidious  manner,  or  else  the  chronic  course  i  interrupted  by  an 
acute  attack  which  leads,  as  the  case  may  be,  to  rec  r  to 

death,  or,  as  a  third  alternative,  leaves  the  organism  in  the  same 
condition  as  before  its  occurrence. 

Death.    When  an  acute  disease  ends  in  death  the  fatal  termination 
may  occur  suddenly,  in  an  unexpected  manner,  or  3lowly  and  pro- 
gressively, preceded  1  >%  more  or  less  prolonged  agony,     [f  oecr< 
is  performed,  macroscopic  or  microscopic  lesion  ometimes 

found.  In  olher  eases  post-mortem  examination  gives  a  negative 
result.  By  taking  into  account  the  various  results  which  may  be 
obtained  the  causes  of  death  may  be  divided  into  three  groupe: 
1.  Mechanical  disorders  or  barriers.  2.  Lesions  of  an  important 
organ.     3.  General  infection  or  intoxie.it ion. 

As  a  striking  illustration  of  the  mechanism  of  death  by  a  mechan- 
ical cause  we  may  mention  diphtheritic  laryngitis.  The  pseudo- 
membrane  developing  in  the  larynx  embarrasses  the  passage  of  air, 
and  may  cause  death,  partly  through  the  reflex  spasm  which  it 
excites.  Likewise,  a  phlegmon  taking  its  origin  in  certain  regions, 
may,  by  its  size  or  by  the  edema  surrounding  it,  mechanically  induce 
a  fatal  termination.  In  these  examples  death  evidently  results  from 
the  obstacle  created  by  the  lesion,  since  if  the  false  membrane  be 
detached  or  the  circulation  of  air  be  re-established  through  intubation 
or  tracheotomy,  or  the  phlegmon  be  opened,  the  disorders  disappear 
immediately. 

The  local  lesion  which  thus  endangers  life  is  not,  however,  the 
work  of  a  microbe,  but  is  due  to  a  reaction  of  the  organism,  which 
seems  to  fight  against  itself.  But  if  Ave  more  closely  investigate 
the  succession  of  the  phenomena,  we  understand  that  the  organism 
has  produced  a  false  membrane  or  a  purulent  focus  in  order  to  pre- 
vent general  impregnation.  The  lesion  thus  created  was  designed 
to  circumscribe  the  morbid  process  and  to  oppose  the  penetration 
of  microbes  or  their  toxins.  The  organism,  however,  is  not  always 
capable  of  proportioning  its  efforts  to  the  work  required.  In  a  good 
many  instances  reaction  exceeds  the  end.  A  microbe  penetrating 
into  the  lungs  induces  an  acute  pulmonary  congestion.  The  vessels 
dilate  in  order  to  facilitate  the  escape  of  fluids  and  cells  which  will 


536  I MECTIOUS  DISEASES. 

arrest  the  development  of  the  parasite.  The  reactionary  pheno- 
mena, however,  are  often  too  intense,  and  may  induce  grave  accidents. 
In  other  cases  the  microbe  reaches  the  surface  of  the  lung  and 
irritates  the  pleura,  which  then  secretes  a  fluid  that  is  often  so 
excessive  in  amount  as  to  necessitate  surgical  intervention  for  its 
evacuation.  .Lastly,  in  certain  instances  reaction  is  not  too  strong. 
It  is  truly  beneficial,  but  it  is  produced  in  particularly  delicate 
localities,  and  for  that  reason  may  prove  dangerous.  Such,  for 
example,  are  congestion,  edema,  and  abscess  produced  in  the  brain. 
Under  these  various  conditions  the  organism  endeavors  to  remedy  the 
immediate  disorders,  but  it  mobilizes  too  great  a  number  of  cells  or 
gives  issue  to  an  excessive  amount  of  fluid. 

Under  such  circumstances,  therefore,  therapeutic  measures  should 
be  directed  to  the  organism  itself,  so  as  to  moderate  the  morbid 
reaction  and  check  the  intense  congestion  which  threatens  to  give 
rise  to  asphyxia  by  reason  of  its  intensity.  In  other  instances,  on 
the  contrary,  we  must  assist  the  organism  in  its  efforts  to  accomplish 
that  part  of  its  work  which  it  is  unable  to  do  alone.  Puncture  of  a 
pleural  collection  or  the  evacuation  of  a  cerebral  abscess  is  not 
medication  against  nature,  but  a  complementary  method  aiding  the 
insufficiency  of  natural  means. 

As  morbid  reactions  may,  on  the  one  hand,  endanger  life  by  their 
excessive  intensity,  on  the  other,  their  insufficiency  may  be  a  new 
cause  of  disorders.  When  a  microbe  develops  it  gives  rise  to  sub- 
stances which  destroy  the  surrounding  cells.  The  destroyed  ele- 
ments are  liquefied  and,  when  possible,  thrown  out.  When  the 
organism  fails  to  remedy  the  imminent  accidents  by  the  various 
means  at  its  disposal,  notably  through  the  accumulation  of  wander- 
ing cells,  or  if  the  leucocytes  be  killed  as  they  arrive  at  the  point  of 
invasion,  a  more  or  less  complete  destruction  of  the  affected  tissue 
will  result.  Gradually  extending,  necrobiosis  may  reach  a  vessel, 
and,  if  the  course  of  the  process  is  rapid,  a  grave  or  fatal  hemorrhage 
occurs  before  a  clot  is  formed.  In  other  cases  an  important  cavity 
is  opened.  For  instance,  the  wall  of  the  intestine  may  be  perforated. 
In  these  various  instances  lesions  which  are  apparently  sufficient 
to  account  for  death  are  revealed  by  the  necropsy. 

As  a  result  of  anatomico-pathological  discoveries  we  have  become 
so  accustomed  to  attach  an  exaggerated  importance  to  anatomical 
lesions  that  our  minds  are  satisfied  when  the  necropsy  detects  a 
morbid  focus  in  some  important  organ.     Let  us  take,  for  example, 


EVOLUTION  OF  INFECTIOUS  DISEASES.  :,.;? 

the  case  of  a  child  dead  of  tneai  les.     During  life  a  murmur 

found  at  the  base  of  one  lung,  and  on  opening  the  cadaver  a  I 
of  bronchopneumonia  is  discovered  at  this  point.  The  mechani  m 
of  death  in  this  instance  appears  to  be  readily  conceivable;  yel 
on  a  little  reflection,  it  will  be  acknowledged  thai  it  i  hardly 
possible  to  attribute  the  filial  termination  to  a  lei  ion  <>  i  mall  ai  not 
to  hinder  hematosis  t<>  any  ,Lrn:ii  degree.  'Mi''  3ame  rea  oning  is 
applicable  to  oilier  organs  as  well  in  those  cases  in  which  multiple 
lesions  an;  found.  In  acute  miliary  inlierculo  i  ,  when  the  tubercles 
have  invaded  the  serous  system  only,  why  has  the  individual  died? 
Pushing  the  question  further,  it  may  be  asked:  Why  has  he  suc- 
cumbed even  when  the  multiple  granules  have  invaded  the  riscera? 
There  generally  remains  sufficienl  intact  parenchyma  to  assure  the 
function  of  the  organ.  It  is  here  that  modern  science  inter 
and  rightly  proclaims  the  r61e  of  toxins  secreted  in  the  dia 
organs  and  leads  to  the  admission  that  death  is  due  to  poisoning. 
This  interpretation  is  confirmed  by  those  cases  in  which  no  manifest 
lesions  are  revealed  by  the  necropsy. 

Let  us  suppose  an  individual  succumbing  to  anthrax.  The  blood 
is  disintegrated,  dark,  and  stick)',  and  the  spleen  is  voluminous  and 
the  other  viscera  congested.  At  times  small  visceral  ecchymoses 
only  are  met  with.  This  is  evidently  somewhat  disappointing.  On 
examining,  however,  a  drop  of  the  blood  or  a  particle  of  the  organs 
under  the  microscope,  innumerable  bacilli  are  observed,  and  thus 
some  light  is  shed  on  the  problem.  Death  is  due  to  general  infection. 
Toussaint  used  to  say  it  was  due  to  an  obstruction  of  the  capillaries 
by  the  bacilli.  But  this  invasion  and  dissemination  of  the  foreign 
elements  does  not  seem  to  be  sufficient  to  explain  the  fatal  termin- 
ation. It  is  neither  by  crowding  the  vessels  nor  by  abstraction  of 
oxygen  or  of  the  materials  necessary  for  cellular  renovation  that  the 
bacteria  have  destroyed  life,  but  by  secreting  soluble  substances 
capable  of  disturbing  the  activity  of  the  cells. 

This  interpretation,  which  may  seem  contestable  as  regards 
anthrax,  is  the  only  one  admissible  in  reference  to  those  diseases  the 
pathogenic  agent  of  which  is  localized  at  a  certain  point  of  the 
organism.  In  diphtheria,  gaseous  gangrene,  and  cholera  the  microbes 
do  not  invade  the  economy.  They  remain  localized  at  a  point  or 
confined  to  the  digestive  canal.  Death  cannot,  therefore,  be  attri- 
buted to  any  other  cause  than  the  soluble  substances  engendered  by 
the  micro-organisms. 


538  IXFECTIO  US  DISEASES. 

It  is  not  enough,  however,  to  say  that  death  is  the  result  of  an 
intoxication.  We  must  endeavor  to  indicate  more  accurately  the 
mechanism  of  a  fatal  termination.  In  certain  cases  lesions  are  found 
which  of  themselves  would  be  sufficient  to  endanger  life.  For 
example,  the  autopsy  reveals  degeneration  of  the  liver  and  kidneys, 
myocarditis/ or  hemorrhages  of  the  suprarenal  capsules.  Chemical 
analysis  shows  the  diminution  or  even  the  absence  of  glycogen  in  the 
liver,  and  microscopical  examination  demonstrates  the  presence  of 
cellular  lesions  in  most  of  the  organs.  It  may  then  be  asked  whether 
these  multiform  alterations  have  not  played  a  part  in  bringing  about 
the  final  result  and  whether  the  autointoxication  arising  from  organic 
insufficiency  has  not  been  added  to  the  microbic  intoxication.  This, 
however,  would  only  displace  the  problem,  for  it  is  at  all  events  to  be 
recognized  that  the  cellular  lesions  are,  in  certain  cases,  too  limited 
to  exert  a  notable  influence.  We  are  thus  brought  again  to  admit 
a  toxic  action.  This  action,  however,  is  not  immediate.  The 
microbic  poisons  do  not  kill  rapidly,  but  a  certain  length  of  time 
elapses  between  the  moment  of  their  introduction  and  the  instant 
when  the  first  responsive  manifestations  appear.  Instead  of  at  once 
arresting  the  nutritive  activity  which  essentially  characterizes  life, 
the  microbic  toxins  disturb  nutrition  by  adulterating  the  intercellular 
medium.  Whether  the  poison  itself  modifies  this  medium,  or  whether 
the  secondary  products  originating  under  the  influence  of  the  toxins 
act  as  a  ferment,  is  a  matter  of  little  importance.  What  is  an 
important  fact,  however,  is  that  even  when  a  fatal  dose  is  at  once 
introduced  into  a  vein,  the  animal  dies  only  after  the  lapse  of 
several  hours.  This  means  that  a  whole  series  of  secondary  modi- 
fications are  produced  through  the  influence  of  the  toxin. 

We  are  thus  led  to  consider  not  the  total  death,  but  the  individual 
death  of  the  parts  of  the  organism — i.  e.,  of  the  cells.  It  might  be 
supposed  that,  under  the  influence  of  toxins,  nutrition  is  equally 
perverted  in  all  parts  of  the  organism;  but  such  a  conception  is 
hardly  admissible.  The  cells  are  disturbed  according  to  a  fairly 
determined  order — those  performing  the  highest  functions  are 
affected  first.  The  nerve  cells  occupj'  the  highest  position,  and 
experimentation  in  accordance  with  clinical  facts  shows  that  it  is 
upon  them  that  the  deleterious  action  of  toxins  is  in  most  cases 
exerted.  The  dynamic  state  of  the  nerve  cells  being  thus  modified, 
it  is  comprehensible  that  an  occasional  cause,  by  producing  in  them 
an  abnormal  agitation,  may  induce  sudden  or  speedy  death.     Other- 


EVOLUTION  OF  TNFEOTIOV     DI8E  I    i:s.  539 

wise,  the  fatal  termination  Bupervenei  gradually  a  the  re  nil  of 
progressive  weakening  of  metabolism.  In  order  to  admit  tl 
different  conceptions  withoul  reservation  we  should  be  exactly 
informed  as  to  the  functional  state  of  the  variou  parts  of  the 
organism  at  the  moment  of  death.  Bere  i  a  mo  I  difficult  question 
which  has  not  as  yet  been  the  subject  of  experimental  stui 

In  brief,  death  as  a  result  of  infection  i-  death  from  intoxication. 

The  inicrol>ic  poisons  ;iceiiiniil;iie  in  the  organism  and  hinder  or 
prevent  normal  cellular  life.  Possibly  they  act  I)}'  forming  combina- 
tions with  the  cellular  protoplasm.  Ii  is  more  probable,  however, 
that  they  affect  the  cells  by  adulterating  the  intercellular  medium. 
The  result  is  a  series  of  functional  disturbances  which  cause  death, 
and  at  the  necropsy  no  lesion,  or  almost  none,  is  found  even  under 
the  microscope.  If  lesions  are  met  with  they  are  too  small  to 
account  for  the  fatal  termination.  If  life  i>  prolonged,  however, 
functional  disorders  induce  anatomie:il  modifications.  Thus  im- 
portant cellular  lesions  are  secondarily  produced  which  play  an 
important  role  in  the  mechanism  of  deferred  death.  Here,  however, 
the  question  is  no  longer  one  of  infection,  but  of  organic  lesions 
evolving  on  their  own  account  and  deriving  no  particular  character 
from  their  origin. 

It  is  well  here  to  call  attention  to  a  mode  of  termination  which  is 
not  rare  in  young  children  and  the  aged.  The  patients  recover 
from  their  infection  and  seem  to  be  entering  upon  convalescence. 
Such  is  not  the  case,  however;  general  debility  rapidly  progresses, 
and  emaciation  becomes  more  pronounced  day  after  day.  Then  the 
intelligence  becomes  dull;  eschars  make  their  appearance,  and  at 
times  slight  fever  manifests  itself  in  the  evening.  After  a  period 
of  time,  varying  from  eight  to  fifteen  dajrs,  death  supervenes  without 
any  other  symptom,  as  a  result  of  post-infectious  cachexia.  Such 
an  evolution  is  observed  after  erysipelas.  We  may.  in  this  con- 
nection, report  the  case  of  a  man,  sixty  years  of  age,  who  entered  our 
hospital  for  an  erysipelas  of  the  face  on  the  twentieth  da}'  of  its 
evolution.  On  the  day  of  admission  his  cutaneous  inflammation 
still  occupied  the  nose,  forehead,  cheeks,  eyelids  and  scalp.  The 
temperature  was  103.5°  F.  (39.8°  C),  accompanied  by  slight  delirium. 
The  urine  contained  no  albumin,  the  liver  was  not  swollen.  Two 
days  after  the  temperature  fell  to  101.7°  F.  (38.5°  C),  and  five  days 
after  his  admission  it  returned  to  normal.  He  seemed  to  have 
recovered  from  the  erysipelas,  but  his  general  state  remained  quite 


540  INFECTIO  US  DISEASES. 

unsatisfactory.  The  temperature  continued  to  fluctuate  about 
98.5°  F.  (37°  C),  and  he  was  becoming  cachectic  quite  rapidly,  and 
thirteen  days  after  his  admission  he  died.  For  the  last  eight  days 
his  temperature  had  been  normal,  and  on  the  day  of  death  it  was- 
only  98.5°  F.  (36.6°  C).  The  necropsy  revealed  no  special  lesion 
capable  of  explaining  the  fatal  termination.  The  lungs,  particularly 
the  right  lung,  were  congested  at  the  bases.  The  heart  presented  a. 
slight  fatty  condition.  The  mitral  valve  was  thickened,  the  aorta 
slightly  dilated  and  atheromatous.  The  kidneys  were  also  sur- 
rounded with  a  thick  layer  of  fat.  The  liver  presented  the  color 
of  chamois  leather,  and  on  section,  violet.  The  weight  of  all  these 
organs  was  less  than  normal.  The  cause  of  this  post-infectious 
cachexia  is  probably  chargeable  to  a  previous  insufficiency  of  the 
organs  concerned  in  the  protection  of  the  organism  against  infections, 
notably  the  kidneys  and  the  liver.  The  toxins  elaborated  by  the 
pathogenic  microbe  are  not  destroyed  or  eliminated  with  gratifying 
rapidity;  hence  impregnation  is  more  profound  than  is  indicated 
by  the  benign  character  of  the  infectious  lesion,  and  its  effects  con- 
tinue after  apparent  recovery.  The  situation  is  the  same  as  in 
certain  animals  brutally  inoculated  with  a  large  dose  of  an  attenuated 
microbe.  If  the  microbe  is  highly  virulent,  the  animal  dies  from 
an  acute  septicemia.  If  moderately  virulent,  it  is  destroyed,  but 
the  toxins  which  are  introduced  with  the  pathogenic  agent  and 
those  which  are  elaborated  by  it  within  the  organism  continue  their 
action  and  give  rise  to  a  fatal  cachexia.  This  is  what  happens 
notably  with  the  streptococcus.  In  fact,  we  have  shown  that  intra- 
venous injection  of  attenuated  cultures  seems  to  produce  no  symp- 
toms, and  then,  after  a  few  days,  the  animals  grow  thin  and  succumb 
in  from  fifteen  to  twenty  or  thirty  days  after  the  inoculation,  in  a 
state  of  an  extraordinary  degree  of  cachexia  and  emaciation.  At 
this  moment  the  microbe  has  disappeared  from  the  organism  and 
cultures  made  from  the  organs  remain  sterile. 


(Ml  A  PTEE    XVI]  I. 
THE  CONSEQUENCES  OF  INI  EC1  EON. 

Apparent  and  Real  Recovery.    Reparation  of  Traumatic  [>    Ion    ando  •  t  ir,,j ^ 

Lesions.    Comparison  between  The  e  Two  Proci     i        I  ol  the  Diffei 

Post-infectious  Visceropathies.     Their  Mechanism.     Their  B volution,     Epithelial 
and  [nterstitial  Visceropathies.     [mportance  ol  Vi  ceral  Sclera  Lficance  of 

SclcroscH. 

Can  an  infection  be  cured  completely?  The  disease  having 
terminated,  can  the  organism  return  to  its  former  state?  Can  all 
the  disorders  that  were  produced  disappear  and  all  the  lesions  be 

repaired?  From  a  practical  standpoint  there  is  no  doubl  as  to  the 
answer  to  this  question.  After  an  infection,  even  though  it  be  grave 
or  prolonged,  health  is  re-established;  the  patient  is  conscious 
having  returned  to  his  normal  state;  years  may  elapse,  and  life  may 
come  to  an  end  without  the  slightest  manifestation  having  been 
observed  which  might  rightly  be  traced  to  the  previous  infection. 
If,  however,  the  question  be  considered  from  a  higher  point  of  view 
a  quite  different  solution  is  reached.  Complete  restoration  of  the 
economy  to  its  previous  state  seems  to  us  impossible.  Recovery 
being  clue  to  modifications  in  the  fluids  and  the  fluids  being  cellular 
secretions,  it  is,  of  course,  necessary  for  changes  to  be  produced  in 
the  mode  of  life — i.  c,  in  the  nutrition  of  the  cells,  in  order  that 
the  infection  may  be  overcome.  If  at  all  possible,  the  return  of  the 
organism  to  its  normal  nutritive  mode  is  to  be  gradually  effected. 
Will  such  be  the  case  in  every  instance?  Observation  teaches  us 
that,  in  a  great  number  of  cases,  nutrition  is  profoundly  and  defi- 
nitely modified.  The  variations  in  the  degree  of  fatness  of  the 
individuals  are,  from  this  standpoint,  quite  demonstrative.  In  some 
cases  obesity,  in  others  an  excessive  emaciation,  is  the  permanent 
result  following  an  infectious  disease.  These  changes  are  readily 
appreciable  after  acute  infections,  such  as  typhoid  fever,  or  even 
after  recovery  from  a  chronic  infection  such  as  tuberculosis.  In 
some  of  these  cases  the  post-infectious  modifications  are  favorable. 
The  infection  having,  so  to  say,  whipped  the  organism  to  greater 
activity,  improves  the  health,  with  the  result  that  certain  ill-deter- 


54:2  I M'ECTIOUS  DISEASES. 

mined  disturbances,  often  attributed  to  diathetic  conditions,  dis- 
appear, and  previous  chronic,  notably  nervous,  affections  are  cured. 
The  reverse  effect,  however,  is  unfortunately  more  frequent.  The 
acute  disease  often  proves  to  be  the  occasional  cause  of  a  series  of 
consecutive  disturbances  and  various  neuroses.  In  certain  cases  the 
consequences'  of  infection  are  so  pronounced  as  to  be  noticeable 
even  by  the  most  superficial  observers.  Not  infrequently,  however, 
they  easily  escape  notice  and  are  very  difficult  of  interpretation. 
As  a  matter  of  fact,  these  consecutive  changes  are  sometimes  so 
slight  that  we  are  compelled  to  assume  their  existence  by  induction 
rather  than  by  observation.  Moreover,  they  may  make  their  appear- 
ance very  tardily;  months  and  years  elapse,  and  when  symptoms 
become  apparent  after  such  long  periods  some  hesitation  is  felt 
in  connecting  them  with  their  true  cause. 

We  must  now  successively  consider  the  consequences  of  local 
lesions  produced  by  toxins  and  general  disturbances  which  may 
develop  under  their  influence.  The  local  action  of  toxins  is  ex- 
pressed, as  is  known,  b}'  degenerations  or  cellular  necrobioses.  The 
most  clearly  differentiated  elements,  which  perform  the  highest 
functions  but  which  are  also  the  most  delicate,  are  first  attacked. 
The  cells  constituting  the  tissues  and  organs  are  not  all  similar. 
All  of  them  do  not  have  the  same  force  of  resistance ;  hence,  in  the 
presence  of  the  same  morbific  cause,  they  do  not  all  react  in  the 
same  manner.  Certain  cells  succumb,  while  some  undergo  alter- 
ations, some  remain  intact,  and  still  others  present  evident  signs 
of  excitation  and  may  abundantly  proliferate.  The  ulterior  fate 
of  the  organ  differs  according  to  the  state  of  these  variously  affected 
cells.  Those  which  have  begun  to  proliferate  may  serve  to  repair 
and  replace  those  which,  being  less  resistant,  have  degenerated  or 
been  killed.  A  perfect  reparation  might,  therefore,  be  expected. 
In  reality,  however,  such  is  not  the  case.  There  is  a  curious  differ- 
ence between  the  reparation  of  traumatic  and  of  infectious  lesions. 
When  a  part  of  an  organ  is  excised,  complete  restoration  is  possible. 
Let  us  suppose  that  even  a  large  piece  of  the  liver  is  cut  off.  If 
the  experiment  is  well  conducted,  if  infection  is  avoided,  repair 
will  be  effected  and  newly  formed  cellular  tissue  will  fill  up  the 
deficit.  If,  on  the  contrary,  the  cellular  destruction  is  the  work  of 
infection,  reparation  will  not  be  as  complete.  A  great  number  of 
the  diseased  cells  will  be  replaced  not  by  similar  cells,  but  by 
sclerotic  tissue.     Microbic  as  well  as  exogenic  poisons  are  capable 


THE  CONSEQUENCES  OF  INFECTION.  :,].; 

of  exerting  the  same  influence.     It  verj  Bmall  doses  of  pbosphorue 
are  administered  to  an  animal,  degeneration  of  its  hepatic  cell    is 
produced,     [f   the  employmenl    of   the   poison    i     then   Btopped, 
cicatrization  takes  place    i.  e.}  a  proliferation  of  connective  ti 
which  replaces  the  dead  cells. 

Not   infrequently,   however,   infection   as    well   at    intoxication 
destroys  only  a  small  number  of  cells.    Their  replacement  would, 

therefore,  seem  easier  Ih.'in  in  c;ises  in  which  traumatil  m  hfl 

1,1  in  dis.'i|)|)e.'ir:i.nce  of  one  fourth  or  one-third  of  the  gland.  I  il  nol 
also  known  that  extirpated  organs  have  completely  regenerated 

when  a  small  fragment  had  been  left?  In  such  cases  reproduction 
of  nearly  all  the  cells  and  of  the  primary  type  has  taken  place, 
although  the  task  of  reparation  seemed  far  more  difficult  than  in 
the  case  in  which  destruction  is  partial  and  disseminated.  This 
fact  proves  that  sclerosis  is  not,  as  might  have  been  believed,  a 
tissue  taking  the  place  of  destroyed  cells.  It  is  necessary  that  this 
destruction  should  present  certain  particular  characters.  This  fact 
may  eventually  be  interpreted  in  several  ways.  The  simplest 
explanation  seems  to  be  the  following:  In  the  case  of  traumatism 
the  excised  cells  are  far  more  numerous,  but  the  remaining  cells  are 
sound;  they  possess  normal  activity:  they  proliferate  and  occupy 
the  place  left  vacant.  On  the  other  hand,  in  the  case  of  infection — 
and  what  we  say  of  infection  is  applicable  to  intoxication — the 
soluble  substances  impregnate  the  whole  gland.  The  cells  which 
first  receive  the  poison  or  those  which  are  less  resistant,  degenerate 
or  are  killed;  others,  although  they  survive  and  are  apparently 
normal,  do  not,  however,  completely  escape  the  influence  of  the 
morbific  cause.  Their  activity  is,  therefore,  disturbed,  and,  although 
the  modification  is  not  expressed  by  any  lesion  appreciable  under 
the  microscope,  it  is  safe  to  assume  that  this  modification  is  sufficient 
to  hinder  proliferation.  It  is  thus  conceivable  that  reparation  is 
the  more  difficult  and  incomplete  the  more  profound  is  infection. 
We  may  repeat  once  more:  sclerosis  is  produced  not  because  the 
destroyed  cells  are  too  large  in  number  (infection  never  causes  the 
disappearance  of  as  many  of  them  as  does  traumatism),  it  occurs 
simply  because  the  remaining  cells  are  not  normal.  The  same  inter- 
pretation is  applicable  to  those  cases  in  which  the  focus  of  destruction 
is  well  limited.  The  neighboring  cells  are  alone  disturbed,  but  these 
are  precisely  the  cells  which  should  proliferate  and  are  incapable 
of  so  doing.     It  is,  therefore,  intelligible  that  an  infectious  lesion. 


544  IXFECTIO  US  DISEASES. 

however  small,  may  produce  more  extensive  disorders  than  a  far 
more  considerable  traumatic  lesion.  The  result  is  that  reparation 
is  less  perfect. 

If  the  lesion  is  well  localized  and  not  very  extensive,  the  resulting 
cicatrices  may  sometimes  produce  no  disturbance.  Such  is  not 
always  the  case,  however,  as  may  be  seen  from  the  frequency  of 
strictures  occurring  in  the  urethra  in  consequence  of  gonorrhea. 
This  illustration  elucidates  the  history  of  organic  lesions.  Viscer- 
opathies  have  long  been  considered  as  diseases.  Imbued  with  the 
false  idea  of  morbid  spontaneousness,  physicians  believed  they  had 
solved  the  nosological  problem  when  they  found  a  cardiac,  renal, 
hepatic,  or  cerebral  lesion.  For  instance,  a  mitral  insufficiency  was 
detected,  and  if  rheumatism  was  not  found  in  the  antecedents  of 
the  patient,  no  investigation  was  made  as  to  the  cause  of  the  lesion. 
At  present  we  know  that  every  disease  is  caused  by  an  external 
agent  and  that  visceral  lesions  are  nothing  else  than  the  conse- 
quences of  previous  diseases.  The  process  occurring  in  the  organs, 
though  of  a  more  complex  character,  is  none  the  less  comparable  to 
that  occurring  in  the  urethra. 

The  pathological  anatomy  of  acute  infections  has  shown  us  that 
cellular  lesions  are  far  more  intense  and  diffuse  than  was  once 
believed.  The  systematic  study  pursued  in  recent  years  with  regard 
to  the  viscera  and  the  tissues  during  infections  leads  us  to  the 
question  how  any  process  of  repair,  even  incomplete,  is  still  possible. 
It  is  true  that  when  visceral  lesions  are  too  extensive,  death  super- 
venes during  the  acute  stage  of  the  disease,  and  less  frequently  it 
occurs  after  the  process  seems  to  be  at  an  end.  We  have  already 
shown  how  the  aged  thus  succumb  to  a  post-infectious  cachexia. 
At  a  less  advanced  stage,  however,  a  return  to  health  seems  to  be 
effected.  The  most  careful  examination  reveals  no  appreciable 
disorder,  and,  for  a  number  of  years,  the  organism  seems  to  have 
returned  to  a  perfectly  sound  state.  Nevertheless,  a  silent  evolution 
is  going  on,  ending  in  visceral  sclerosis.  The  lesion  may  exist  for 
a  very  long  period  of  time  without  being  expressed  by  any  symptom. 
This  is  owing  to  the  fact  that  the  organs  contain  a  far  greater  number 
of  cells  than  is  necessary  for  life.  It  may  be  assumed  that  40  to  50 
per  cent,  of  the  glandular  tissues  may  be  suppressed  without  bringing 
about  any  disturbance.  One-third  of  the  liver,  a  whole  kidney,  even 
a  whole  lung,  may  be  extirpated  without  great  inconvenience.  It 
is  therefore  intelligible  that  a  visceral  lesion  may  evolve  during  years 


THE  CONSEQUENCES  OF  INFECTION.  :,\:t 

without  producing  any  symptom.  The  affection  i  in  a  tate  of 
latency,  and  will  be  revealed  later,  either  by  signs  detected  by 
methodic  exploration  or  |>y  the  fact  thai  the  un  table  equilibrium 
of  the  sanitary  condition  resulting  from  the  visceropathy  i  dit  turbed 
l>y  some  intercurrent  and  maybe  unimportanl  cause.  The  ymp- 
toms  may  thus  make  their  appearance  suddenly  or  progre  ively 
on  the  occasion  of  a  cold,  traumatism,  fatigue,  an  error  of  diet,  or 
a  new  infection.  It  must  also  he  remembered  thai ,  in  certain  C 
the  visceral  affection  always  remains  in  a  state  of  latency,  and  will 
be  disclosed  only  at  the  necropsy.  In  other  instances  the  visceral 
affection  is  revealed  in  a  sudden  manner,  causing  sudden  death. 

The  necropsy  in  such  cases  surprises  the  physician  by  revealing 
profound  lesions  which  had  remained  so  long  in  a  state  of  latency 
without  manifesting  any  clinical  disturbances. 

The  organic  affections  which  appear  thus  as  the  consequence 
notably  of  previous  infectious  diseases,  may  be  divided  into  two 
great  classes.  In  one  of  them  epithelial  lesions  predominate;  in  the 
other,  sclerotic  lesions.  Hence,  the  classical  division  of  affections 
into  parenchymatous  and  interstitial,  a  division  which  seems  to  be 
justified  both  by  clinical  observation  and  pathological  anatomy.  ( hi 
investigating,  however,  the  causes  which  have  led  to  the  develop- 
ment of  these  two  distinct  processes,  we  find  the  same  etiology 
and  the  same  infections  responsible  for  both  kinds  of  changes. 
We  are  thus  led  to  the  idea  that  visceral  lesions  are  everywhere  and 
always  at  first  characterized  by  a  diffuse  inflammation,  and  this 
idea  finds  a  solid  basis  in  anatomico-pathological  studies.  In  view 
of  the  facts  hitherto  reported,  we  reach  the  conclusion  that  microbic 
toxins  first  give  rise  to  epithelial  degeneration,  which  is  soon  followed 
by  inflammatory,  epithelial,  and  interstitial  reactions.  At  this 
moment  the  process  is  diffuse.  Later,  when  the  acute  phenomena 
have  passed,  a  chronic  evolution  takes  place  in  either  direction. 
One  of  the  elements  predominates,  and  the  result  of  the  processes 
which  were  at  first  identical,  is  either  a  parenchymatous  or  a  sclerotic 
inflammation.  It  is  more  difficult  to  determine  the  causes  which 
intervene  and  direct  the  anatomical  evolution.  Two  factors,  as 
always,  may  be  admitted:  the  toxins  induce  degenerative  or  simply 
irritative  lesions — i.  c,  cause  the  death  of  the  highly  organized  cells  or 
stimulate  the  proliferation,  according  to  (a)  the  degree  of  resistance 
of  the  subject,  or  (6)  the  degree  of  activity  of  the  microbe.  It  is 
conceivable  that,  in  the  former  instance,  the  elements  that  are  killed 

35 


546  INFECTIOUS  DISEASES. 

may  not  be  replaced  by  any  other  than  connective  tissue.  In  the 
latter  case,  on  the  contrary,  the  perishing  cells  are  smaller  in  number 
and  the  vacancies  left  are  filled  up  by  the  neighboring  cells  the 
activity  of  which  is  increased.  Reparation  would  therefore  be 
perfect,  if  there  was  only  cellular  hyperactivity.  But  pathologic 
histology  establishes  that  along  with  this  overactivity  there  is  a 
nutritive  deviation.  In  this  connection  our  researches  concerning 
the  modifications  of  the  thyroid  gland  are  quite  demonstrative. 
We  have  shown  that,  in  the  most  varied  infections,  the  following 
three  phenomena  are  always  present :  death  of  some  cells  and  degen- 
eration or  increased  activity  of  certain  others.  In  some  cases  the 
two  last  processes  coexist;  the  nucleus  is  multiplied  while  the  pro- 
toplasm degenerates.  But  the  modification  of  the  secreted  fluid 
proves  the  profound  disorder  of  the  cells.  Colloid  matter  presents 
reactions  which  enable  us  to  follow  under  the  microscope  the  histo- 
chemical  changes  occurring  in  it.  It  is  very  easy  to  thus  prove  the 
functional  disturbances.  It  is  therefore  conceivable  that  when  the 
infection  is  terminated,  three  different  processes  may  ensue:  In 
some  cases  degeneration  will  predominate,  in  others  proliferative 
overactivity,  and  in  still  other  cases  sclerosis  will  replace  the  dead 
elements.  In  the  last  instance  the  process  has  been  too  intense; 
the  cells  in  the  neighborhood  of  those  that  have  succumbed  are 
themselves  too  much  affected  to  proliferate  and  occupy  their  place. 
Sclerosis,  therefore,  seems  to  us  to  be  the  termination  of  intense, 
extensive,  or  prolonged  inflammatory  processes.  Let  us  again  take 
urethral  stricture  as  an  example.  In  cases  of  gonorrhea  occurring 
only  once  and  having  been  rapidly  cured,  stricture  is  exceptional. 
The  cells  adjacent  to  those  destroyed  have  succeeded  in  taking  the 
place  of  the  dead.  In  gonorrheas  of  long  duration  stricture  is  the 
rule,  since  the  cells  destroyed  are  too  large  in  number,  and  those 
surrounding  them  are  too  deeply  affected  to  establish  normal  rela- 
tions.   A  cicatrix,  that  is,  sclerotic  tissue,  is,  therefore,  produced. 

The  sclerotic  tissue  destined  to  fill  up  the  vacancies  left  by  the 
dead  cells  must  be  considered  as  a  tissue  of  replacement.  Whether 
it  be  developed,  as  is  generally  held  to  be  the  case,  at  the  expense 
of  the  cells  of  connective  tissue,  or  is  progressively  produced  by 
hypertrophy  of  pre-existing  fibres,  as  seems  to  be  the  case  in  certain 
instances,  it  is  always  destined  to  remedy  immediate  accidents. 
This  sufficiently  indicates  that  we  reject  the  existence  of  primary 
scleroses.     The  connective  tissue  alteration  is  always  preceded  by  a 


THE  CONSEQUENCES  OF  INFECTION,  r,\7 

lesion  of  the  more  highly  differentiated  elements.  In  other  word  . 
scleroses  are  always  of  epithelial  origin.  Lei  u  cod  ider  an  organ 
in  which  scleroses  have  often  been  studied)  for  example  the  kidney. 
An  attempl  was  made  to  admit  two  kinds  of  nephrite  ,  namely, 
epithelial  and  interstitial,  the  latter  indicating  clerosi  from  the 
first.  A  special  etiology,  pathogenesis,  and  symptomatology  had 
been  assigned  to  each  of  these  two  affections.  A  change  was  little 
by  little  produced  in  this  conception.  It  was  recognized  thai  '-very 
case  of  nephritis  begins  in  the  more  highly  organized  element*  and 
that  the  process  soon  extends;  so  thai  nephritis  is  primarily  diffuse, 
and  Inter  on  evolves  toward  various  anatomico-clinical  type-,  the 
two  extremes  of  which  are  represented  by  the  large  white  kidney, 
in  which  the  epithelial  lesions  predominate,  and  by  the  small  red 
kidney,  in  which  the  sclerotic  lesions  prevail.  Thus  are  constituted 
sharply  distinguished  affections  which  must  be  separated  in  ana- 
tomical and  clinical  descriptions.  The  point  of  departure,  however, 
is  the  same  in  all.  The  final  result  differs  because  all  organisms 
are  not  similar. 

The  same  conception  is  applicable  to  hepatic  cirrhoses.  The 
origin  must  be  looked  for  in  a  primary  lesion  of  the  hepatic  or  the 
biliary  cells.  The  idea  of  connecting  atrophic  cirrhosis  with  a 
primary  alteration  of  the  portal  vein,  wrhich  is  still  held  by  some 
authorities,  is  based  upon  incomplete  anatomical  study.  It  is  at 
present  demonstrated  that  the  process  is  not  as  systematic  a?  was 
once  believed.  Sclerosis  develops  simultaneously  around  the  portal 
and  suprahepatic  veins  and  forms  bands  so  irregular  as  to  defy  all 
topographical  description.  On  the  other  hand,  a  sclerotic  lesion  is 
never  seen  to  diffuse  toward  adjacent  parts.  It  is,  therefore,  prob- 
able that  poisons  or  microbes  circulating  in  the  portal  vein  produce 
primary  alterations  in  the  hepatic  cells.  The  marginal  cells  are 
the  most  profoundly  influenced  and  the  first  to  be  affected;  next 
the  central  cells,  which  the  blood  reaches  after  passing  through  the 
capillaries.  Thus  the  topography  of  the  sclerotic  lesions  is  explained. 
In  most  cases  the  venous  alterations  seem  to  be  of  a  secondary 
character.  It  must,  however,  be  admitted  that  they  may  some- 
times be  primary.  They  may  then  produce  sclerosis,  because  the 
circulatory  disorders  disturb  the  nutrition  of  the  cells.  Even  in 
these  cases  the  sclerotic  process  is  not  an  irradiation  of  the  peri- 
phlebitis. It  is  consecutive  to  a  degenerative  alteration  of  the 
hepatic  cells. 


548  INFECTIOUS  DISEASES. 

It  would  be  easy  to  present  analogous  considerations  in  reference 
to  other  glands  and  various  tissues,  and  thus  show  that  sclerosis  is 
always  designed  to  fill  up  vacancies. 

Sclerosis  of  the  nervous  tissue  seemed,  for  a  time,  to  be  an  excep- 
tion. In  reality  there  has  been  an  error  of  interpretation  in  this 
matter.  It  is  at  present  known  that  scleroses  of  the  neuroglia  do 
not  enter  into  the  group  of  true  scleroses.  The  neuroglia  does  not 
represent  connective  tissue.  It  is  an  ectodermic  production,  a 
nervous  tissue.  It  is  not  strange  if  systematic  lesions  not  obe3dng 
the  rules  above  reported  are  produced  in  this  tissue.  The  process 
is  a  special  one  quite  different  from  true  or  mesodermic  sclerosis. 

Although  infectious  diseases  influence  the  entire  economy,  the 
lesions  resulting  from  this  influence  must  be  diffuse.  Generalized 
sclerosis  affecting  the  tissues  and  viscera  are  observed  in  certain 
instances.  The  ensemble  of  these  facts  is  known  under  the  name 
of  arteriosclerosis.  With  or  without  good  reason,  a  predominating 
part  is  thus  attributed  to  the  arterial  system  in  the  genesis  of  these 
disorders.  The  conception  is  not  groundless.  The  microbic  toxins 
carried  by  the  blood  current  must  first  impregnate  the  vascular 
walls.  Even  when  arteriosclerosis  is  generalized,  however,  it  pre- 
dominates at  certain  points.  Hence  a  cardio-aortic,  a  renal,  and  a 
cerebral  sclerosis  have  been  described.  Finally,  in  a  certain  number 
of  cases,  the  process  seems  to  be  different,  although  I  hold  it  to  be 
of  the  same  order;  the  arteries  are  slightly,  if  at  all,  affected;  a 
single  viscus  is  injured.  This  single  visceral  sclerosis  must  be 
classed  with  multiple  organic  sclerosis.  It  is  always  the  same 
process,  progressing  in  an  identical  manner  and  depending  upon  a 
similar  cause.  It  is  in  all  cases  the  result  of  toxi-infection.  It  is 
intelligible, however,  that  the  morbid  localizations  and  post-infectious 
sequels  may  differ  according  to  the  intensity  of  the  infectious  process, 
the  responsive  aptitudes,  and  the  inborn  or  acquired  predisposition 
of  the  individual.  This  is  sufficient  indication  that  we  do  not  class 
visceral  scleroses  with  arteriosclerosis.  We  believe  that  the  two 
orders  of  lesions  progressing  side  by  side  depend  upon  a  common 
cause.  Sclerosis  of  the  arteries  and  that  of  the  viscera  are  two 
simultaneous  effects  of  the  same  cause.  The  bond  existing  between 
arteriosclerosis  and  visceral  scleroses  is  not  one  of  subordination 
of  the  latter  to  the  former.  The  frequency  of  this  association  is 
due  to  the  action  of  the  same  cause  upon  similar  tissues.  To  isolate 
the  arterial  alterations  from  the  entire  process  in  order  to  make  of 


THE  CONSEQUENCES  OF  INFECTION.  549 

these  the  cause  of  visceral  alterations  is  to  make  an  artificial  dis- 
sociation which  is  in  nowise  necessary  for  explaining  the  patho- 
genesis of  these  Lesions. 

Scleroses,  whether  arterial  or  visceral,  may  begin  in  childhood 
on  the  occasion  of  a  firs!,  infectious  di  ea  e  or  imple  digestive  di  - 
turbances  the  importance  of  which  is  jusl  being  appreciated.  The 
numerous  fermentations  which  80  easily  occur  in  nun  lingE  produce 
alterations  in  the  entire  organism,  and  may  evidently  become  the 
starting  point  of  a  number  of  organic  affections  the  origin  of  which 
often  remains  undiscovered.  I!  is  conceivable,  however,  that 
scleroses  become  more  frequenl  as  the  individual  advance-  in  wi<-. 
The  aged  are  almost  always  affected  by  it.  It  is  quite  difficult, 
however,  to  determine  the  part  due  to  the  infection.  Visceral  or 
arterial  scleroses  are  the  termination  of  all  pathogenic  causes  which 
have  acted  upon  the  organism  and  which  are  almosi  always  multiple. 
Exogenic  intoxications  (alcoholism,  saturnism)  and  endogenic  intox- 
ications (autointoxications)  are  superadded  to  infectious  intoxi- 
cations and  give  rise  to  alterations  which  end  in  sclerosis.  The 
organic  lesion  thus  constituted  preserves  no  character  of  its  origin. 
On  the  contrary,  it  acquires  a  perfect  autonomy,  progresses  on  its 
own  account,  and  in  its  turn  engenders  disorders  which  are  always 
the  same  regardless  of  their  point  of  departure.  This  is  the  reason 
why  physicians  have  long  believed  in  the  existence  of  diseases  of  the 
organs  when  in  reality  they  were  nothing  more  than  organic  affec- 
tions, more  or  less  tardy  consequences  of  previous  diseases. 

It  is  thus  intelligible  that  the  histor}'  of  the  consequences  of 
infections  may  be  at  times  of  greater  importance  than  the  history 
of  the  infections  themselves.  Anything  that  is  known  as  diseases 
of  organs  may  be  the  tardy  consequence  of  an  infectious  process. 
The  reason  visceropathies  are  not  more  serious  and  frequent  is  that 
the  means  of  defense  and  of  compensation  at  the  disposal  of  the 
organism  are  extremely  numerous. 

If  we  consider  in  their  entirety  the  modifications  produced  by 
infection  in  organs  and  tissues  we  see  that  it  is  possible  to  classify 
them  under  three  headings :  modifications  expressing  increased  func- 
tional activitj';  modifications  in  the  structure  of  the  cellular  elements 
and  modifications  in  texture — i.  c,  changes  in  their  mutual  ordi- 
nation. 

Increased  functional  activity  represents  a  return  of  the  organism 
to  a  former  state  of  its  evolution.    It  is  a  kind  of  rejuvenation  which 


550  ISFECTIOUS  DISEASES. 

is  particularly  appreciable  in  the  bone-marrow,  but  which  is  no  less 
manifest  when  chemical  anatysis  is  applied  to  other  tissues.  Infec- 
tion thus  arouses  functions  which  seem  to  be  extinct.  But  this 
favorable  occurrence  is  calculated  to  remedy  immediate  accidents 
only.  By  adding  the  favorable  and  unfavorable  effects,  we  find  that 
the  latter  exceed.  This  conclusion  suggests  a  practical  consequence. 
Infection  being  so  dangerous,  even  when  slight,  not  so  much  on  its 
own  account  as  by  reason  of  its  remote  consequences,  we  must  be 
extremely  circumspect  in  matters  of  bacteriotherapy.  Even  when 
no  immediate  disturbance  becomes  manifest  we  may  ahvays  suspect 
that  the  injection  of  attenuated  microbes  or  of  toxins  may  be  the 
cause  of  some  tardy  lesions.  This  remark  is  applicable  to  bacterio- 
therapy procedures  as  well  as  to  vaccinations.  We  shall  again  refer 
to  this  method  in  treating  of  the  effects  of  vaccinations. 


CH  A  PTEB    X  I  X. 
MECHANISM  OF  [MMUNITY  AND  OF  PREDISPOSITION. 

Importance  of  Physical  and  Chemical  Modification  oi  thi  Organi  m  Germicidal  Prop- 
erties of  the  Fluids.  History,  Natural  Immunity.  Action  of  the  Serum  of  Normal 
Animals  upon  the  Development,  Morphology,  and  Virulence  of  Microbe       Germi- 

cidal  Actii f  tin-  Serum  of  Vaccinated    Animal        Action  of  the  Serum  upon  the 

Morphology  of  Microbes.  Agglutinating  Power.  Attenuating  Power  of  ii"  Serum. 
Antitoxic  Properties.  Passage  of  Active  Substance  into  the  Secretion  Germi- 
cidal Properties  of  the  Tissues.    Modification    of  the  Serum  in  Animal    Predi  | 

to   Infections.      Modifications  of   the  Scrum   in   the  <  Im- 

portance  and   Significance   of    Modification*-    in    tic    fluid-        Nature   and    Origin   of 

Different  Active  Substances  Contained  in  Serum-      Conclu  •••■ding  the 

Mechanism  of  Immunity. 

The  numerous  researches  pursued  upon  the  interesting  subject 
of  the  mechanism  and  predisposition  of  immunity  have  considerably 

elucidated  certain  points  of  this  important  question  of  general 
pathology.    The  results,  however,  have  been  so  unexpected  or  so 

contradictory  as  to  give  rise  to  spirited  controversies.  The  question, 
perhaps,  appears  to  be  more  obscure  than  it  really  is,  for  the  reason 
that  a  simple  formula  has  been  sought  to  explain  complex  facts. 

Immunity  is  the  result  of  multiple  conditions.  Therefore,  ex- 
clusive theories  are  necessarily  insufficient.  Unfortunately  the 
investigation  of  causes  which  explain  the  resistance  to  infections  is 
surrounded  by  great  difficulties,  and  the  explanation  of  experimental 
results  is  but  seldom  satisfactory. 

Everyone  is  acquainted  with  the  famous  experiment  of  Pasteur, 
who  subjected  a  chicken  to  cold  by  plunging  it  into  water.  The 
chicken,  which  was  until  then  refractory  to  anthrax,  became  sus- 
ceptible to  the  disease.  The  conclusion  that  the  chicken  has  an 
organic  temperature  too  high  to  favor  the  development  of  the 
bacillus  anthrads  seems  evident.  When  this  temperature  is  lowered 
immunity  is  abolished.  The  same  explanation  holds  good  with  an 
inverse  experiment.  A  frog  is  immune  from  anthrax  infection 
because  its  temperature  is  too  low.  When  this  animal  is  heated. 
as  was  done  by  Gibier,  it  contracts  the  infection.  These  experi- 
ments appear  to  be  very  simple  and  easy  of  explanation.  In  reality, 
however,   the   facts   are   highly   complex.     When   we    modify   the 


552  IXFECTIO  US  DISEASES. 

organic  temperature  of  an  animal  we  create  a  whole  series  of  dis- 
turbances. We  change  the  chemical  state  of  the  fluids  and  tissues; 
we  completely  transform  the  sensibility  of  the  nervous  system,  the 
activity  of  the  circulation,  respiration,  and  nutritive  exchanges. 
We  thus  cause  an  incalculable  number  of  modifications,  and  do  not 
know  which  play  the  most  important  role  in  the  final  result.  The 
fact  that  the  pigeon,  the  temperature  of  wThich  is  about  the  same 
as  that  of  the  chicken,  quite  easily  contracts  anthrax  infection, 
proves  that  the  high  temperature  of  the  chicken  is  not  the  cause 
of  its  immunity.  On  the  other  hand,  the  resistance  of  the  frog- 
does  not  depend  upon  its  low  temperature,  since,  at  least  during 
summer,  the  bacillus  anthracis  readily  develops  at  the  surrounding 
temperature,  and  the  toad,  the  temperature  of  which  is  near  that 
of  the  frog,  does  not  enjoy  the  same  immunity.  Finally,  we  have 
made  the  following  experiments  which  seem  to  us  conclusive: 
Frogs  were  placed  in  an  incubator  for  two  days.  They  were  then 
immersed  in  cold  water  and  inoculated  with  anthrax.  Several  of 
them  succumbed  to  the  infection,  although  their  temperature  had 
fallen  to  its  normal  degree.  It  is,  therefore,  certain  that  by  varying 
the  surrounding  temperature  we  act  upon  the  entire  organism;  we 
modify  its  sensitiveness  to  living  microbes  and  toxins,  just  as  we 
modify,  under  similar  conditions,  its  sensitiveness  and  its  resistance 
to  vegetable  alkaloids.  In  the  latter  instance  there  is  no  question 
of  favoring  or  hindering  the  development  of  the  pathogenic  agent. 
The  result  evidently  depends  upon  dynamic  modifications  of  the 
organism. 

The  cause  of  resistance  and  of  predisposition  must,  therefore,  be 
sought  for  in  the  changes  presented  by  living  beings.  Numerous 
experiments .  pursued  in  recent  years  have  shed  light  upon  these 
modifications  of  the  organism.  According  to  some  authorities 
immunity  is  due  to  a  chemical  state  of  the  fluids  and  tissues — a 
chemical  state  hindering  the  development  of  bacteria,  disturbing 
their  functions,  diminishing  their  virulence,  and  neutralizing  their 
toxins.  This  is  the  germicidal  or  antitoxic  theory.  According  to 
others,  immunity  depends  upon  a  dynamic  state  of  the  cells  which 
are  supposedly  capable  of  destroying  the  microbes.  This  is  the 
vital  theory,  the  phagocytic  theory.  These  theories  have  long  been 
and  are  still  being  discussed.  I  have  always  contended  that  no 
exclusive  opinion  should  be  held  regarding  these  questions. 

Predisposition  and  immunity  are  complex  properties ;  they  are  due 


MECHANISM  OF  IMMUNITY  AND  OF  PREDISPOSITION 

to  multiple  factors,  some  of  which  are  ju  I  becoming  known.    It 
is  evident  from   facts  hitherto  observed   thai    immunity 
as  predisposition    cannot  be  explained    by  an  exclu  ive  doctrine. 
In  other  words,  it  seems  to  me  u  elet    to  oppo  e  th<  greal 

theories  to  each  oilier.  I!  is  better  to  endeavor  to  harmonize  them 
and  to  elucidate  the  relations  existing  between  them.  I  hope  to 
succeed  in  showing  thai  the  muds  play  an  importanl  rdle  by  weaken- 
ing the  pathogenic  germs  and  by  diminishing  their  resistance.  They 
thus  favor  phagocytosis.  On  the  other  hand,  the  fluids  being  pro- 
ducts of  the  cells,  all  modifications  in  ih»'  organic  fluid*  require  a 
previous  modification  in  the  figurate  elements.  Here  is  a  aewpoinl 
of  contact  between  the  so-called  humoral  and  cellular  doctrines 
which,  at  first  sight,  appear  so  much  a1  variance. 

Action  of  Fluids  upon  Bacteria. 

History.     If  a  certain  amount  of  a  culture  is  injected  into  the 

veins  of  an  animal  and  then  blood  drawn  several  limes  from  the 
animal,  and  microbes  looked  for,  it  is  seen  that  the  number  of  microbes 
rapidly  diminishes.  At  the  end  of  a  few  hours  the  blood  becomes 
sterile.  The  microbes  accumulate  in  the  organs  in  which  they 
vegetate  and  from  which  they  again  invade  the  blood  during  the 
last  moments  of  life.  This  interesting  result,  pointed  out  by  Fodor1 
and  by  Wyssokowitsch,2  was  confirmed  by  a  great  number  of  experi- 
menters, and  at  present  seems  to  be  indisputable.  By  what  mechan- 
ism does  the  blood  free  itself  of  the  parasites  introduced  into  the 
circulation?  In  a  thesis  written  under  the  inspiration  of  Prof. 
Schmidt  and  defended  in  Dorpat  in  1884,  Grohmann  established 
that  the  blood  modifies  the  vitality  of  microbes  sown  in  it.  The 
anthrax  bacillus  particularly  becomes  thus  attenuated  to  the  point 
of  being  incapable  of  killing  a  rabbit.  The  question  was  taken  up 
by  Fodor.  By  introducing  the  bacillus  anthracis  into  the  blood 
drawn  from  a  rabbit  immediately  after  it  was  killed,  this  author 
found  that  the  number  of  the  bacteria  progressively  diminished. 
Subsequently,  after  a  variable  lapse  of  time,  a  few  microbes  which 
had  escaped  the  destructive  action  of  the  blood,  finally  got  the  upper 

1  Fodor.    Die  Fahigkeit  des  Blutes  Bacterien  zu  vernichten.    Deutsche  med.  Wochen- 
schrift,  1SS7. 

2  Wyssokowitsch.     Ueber  das  Schicksal  der  in's  Blut  injicirten  Mikroorganismen. 
Zeitschrift  f.  Hygiene,  1887. 


554  IXFECTIO  US  DISEASES. 

hand  and  succeeded  in  developing.  The  works  of  Fliigge1  and  his 
disciples,  Nuttal  and  Nissen,  however,  drew  attention  to  this  highly 
important  question.  Their  researches  showed  that  various  microbes 
when  sown  in  the  blood  undergo  therein  at  first  a  degeneration 
clearly  appreciable  by  microscopic  examination.  A  great  many  of 
the  bacteria  are  destroyed,  while  others  persist  and  may  again 
vegetate  at  the  end  of  a  variable  period  of  time. 

The  researches  above  cited,  notwithstanding  their  undoubted 
interest,  are  open  to  some  objections.  It  was  remarked  that  the 
resistance  of  an  animal  is  not  always  related  to  the  germicidal  power 
of  its  blood.  Thus,  Nuttal  noted  that  the  blood  of  the  rabbit 
exerted  upon  the  anthrax  bacillus  a  more  marked  destructive  action 
than  did  the  blood  of  the  dog.  There  is  yet  a  graver  criticism  to  be 
made.  The  blood  employed  for  the  cultures  contained  figurate 
elements :  hence  it  was  possible  that  the  destruction  of  the  microbes 
w^as  partly  accomplished  by  the  blood  cells.  Although  the  majority 
of  the  degenerated  bacteria  were  found  outside  the  leucocytes,  it 
might,  nevertheless,  be  supposed  that  the  modification  was  due  to 
some  soluble  substance  derived  from  these  elements.  By  heating 
the  blood  between  122°  and  131°  F.  (50°  and  55°  C),  we  see  that  it 
loses  its  germicidal  action,  a  fact  which  may  be  due  to  the  death 
of  the  figurate  elements  as  well  as  to  chemical  modification.  A  very 
ingenious  experiment  of  Petruschky,  however,  seemed  to  demon- 
strate that  the  germicidal  action  of  the  fluids  is  real.  By  introducing 
beneath  the  skin  of  frogs  virulent  bacteria,  and  by  protecting  them 
against  the  phagocytes  by  means  of  a  parchment  membrane,  this 
author  found  that  the  microbes  were  attenuated  and  destroyed. 
There  is,  therefore,  no  escape  from  admitting  the  action  of  the 
interstitial  fluids  which  alone  had  been  able  to  diffuse.  The  experi- 
ments, however,  which  dissipated  all  doubt  are  due  to  Behring2  and 
Buchner.  These  authors  operated  not  only  with  total  blood,  but 
also  with  serum,  namely,  with  a  fluid  deprived  of  cells,  and  demon- 
strated that  this  fluid  possesses  notable  germicidal  properties. 
Buchner  further  recognized  that  these  properties  diminish  or  disap- 
pear when  the  serum  is  heated  for  an  hour  at  a  temperature  of  131°  F. 
(55°  C),  or  when  its  nutritive  powrer  is  increased  by  the  addition  of 

1  Fliigge.  Studien  iiber  Abschwachung  virulenter  Bacterien  unci  die  erworbene 
Immunitat.     Zeitsehrift  f.  Hygiene,  1888. 

2  Behring.  Ueber  die  Ursache  des  Immunitat  von  Ratten  gegen  Milzbrand.  Central- 
blatt  f.  klinische  Medicin,  1888. 


MECHANISM  OF  IMMUNITY  AND  OF  PREDISPOSITION 

peptones,  or  by  submitting  the  total  blood  to  a  erie  ol  con- 
gelations and  meltings,  operations  which  de  troy  the  red  blood 
corpuscles  and  liberate  their  contents. 

Stimulated  by  these  works,  a  great  numbei  oi  i  Kperimentei  took 
up  the  study  of  the  germicidal  power  of  normal  blood.  It  will  suffice 
to  cite  the  names  of  Fodor,  Buchner,  Behring,  Karlinski,  Stern, 
Bankin,  Ogata,  Jasuhara,  Sanarelli,  Phi  alix,  Gioxa,  and  Guarnieri. 
While,  however,  numerous  facts  demonstrated  thai  under  normal 
conditions  the  serum  possesses  germicidal  propertie  .  are  the  latter 
increased  in  vaccinated  animals?  The  majority  of  authors  who 
first  attempted  to  solve  this  question  answered  negatively.  They 
took  ground  on  the  fad  thai  microbes  develop  in  bouillon  prepared 
with  the  tissues  of  refractory  animals.  While,  on  the  one  hand, 
Schottelius  noticed  that  the  bacillus  of  swine  erysipelas  vegetates 
with  difficulty  in  culture  media  prepared  with  the  muscles  of  ani- 
mals which  have  died  of  this  affection,  on  ihe  other  hand,  Bitter 
reached  an  entirely  different  result.  In  all  eases,  however,  the 
tissues  were  submitted  to  some  alteration,  and  we  know  at  present 
that  heating  destroys  the  germicidal  properties  of  albuminoid  .-lib- 
stances. 

In  order  to  realize  a  conclusive  experiment,  it  was  necessary  to 
study  comparatively  the  development  of  microbes  in  the  fluid-  of 
normal  and  of  vaccinated  animals.  A  first  endeavor  in  this  direction 
is  that  of  Metchnikoff,1  who  found  that  the  anthrax  bacillus  was 
attenuated  in  the  blood  of  vaccinated  sheep;  but  he  experimented 
with  total  blood,  that  is,  blood  containing  figurate  elements,  and  he 
attributed  the  effect  which  he  observed  to  the  action  of  the  latter. 
Sometime  later,  Gamaleia  showed  that  during  the  anthrax  fever 
and  the  fourteen  days  following  it  the  aqueous  humor  is  modified. 
If  the  anthrax  bacillus  is  sown  therein  the  microbe  develops  under 
a  new  form  and  loses  part  of  its  virulence.  According  to  this  author. 
however,  this  germicidal  state  is  transitory;  it  disappears  while 
immunity  persists. 

We  then  took  up  the  study  of  the  question  and  cultivated  com- 
paratively microbes  on  the  serum  of  non-vaccinated  animals  and  oi 
animals  vaccinated  either  against  the  bacillus  pyocyaneus,8  or  the 

1  Metchnikoff.    Sur  1 'attenuation  ties  bacteridies  charbonneuses.    Annates  de  l'Institut 

Pasteur,  1SS7. 

2  Charrin  et  Roger.  Note  sur  le  developpement  des  microbes  pathogenes  dans  le 
serum  des  animaux  vaccines.     Soci&te'  de  biologic.  1889. 


556  INFECTIOUS  DISEASES. 

bacillus  of  symptomatic  anthrax.1  In  both  instances  we  observed 
that,  as  a  result  of  vaccination,  the  serum  became  a  bad  culture 
medium  for  the  microbe  against  which  the  animal  was  protected. 
These  results  were  soon  afterward  confirmed  hy  Behring  and  Nissen.2 

The  serum  of  vaccinated  animals  acts,  however,  not  only  upon  the 
numerical  development  of  microbes,  but  is  capable  also  of  modifying 
the  forms  of  bacteria  which  resist  and  finally  succeed  in  multiplying. 
It  exerts  upon  them  an  agglutinating  action,  modifies  their  functions, 
and  finally,  as  I  have  demonstrated  with  regard  to  the  streptococcus,3 
it  diminishes  their  virulence.  All  these  influences  are  unfavorable 
to  the  microbe  and  may  be  united,  as  was  proposed  by  Bouchard, 
under  the  general  name  of  germicidal  properties.  The  expression 
is  not  taken  in  its  strict  etymologic  sense  f  it  may  only  be  opposed 
to  that  of  antitoxic  property,  which  is  applied  to  the  discovery  of 
Behring  and  Kitasato.5  As  is  known,  these  authors  demonstrated 
that  the  organism  secretes  antitoxins  capable  of  suppressing  or 
neutralizing  the  action  of  toxins.  The  antitoxic  power,  whether 
exercised  upon  the  toxin,  bj?-  destroying  it,  or,  what  is  more  likely, 
upon  the  economy  by  increasing  its  resistance,  completes  the  germ- 
icidal power  in  the  defense  of  the  organism. 

Here,  therefore,  are  a  series  of  facts  showing  that  vaccination 
produces  in  the  organism  a  number  of  chemical  modifications  which 
must  play  an  important  role  in  its  resistance.  But  a  new  question 
has  been  raised  by  the  study  of  morbid  predispositions.  Are  the 
germicidal  properties  of  the  fluids  diminished  in  an  animal  in  which 
the  resistance  to  the  virus  is  diminished?  The  experiments  which 
we  have  pursued  upon  this  subject  and  those  published  by  Bakunin 
and  Boccardi,  Bastin,  and  Montuori  enable  us  to  answer  in  the 
affirmative.  Thus,  it  may  be  stated  that  the  germicidal  properties 
of  the  blood  vary  with  the  receptivity  of  the  animals.    They  increase 

1  Roger.  Nouvelles  recherches  sur  les  propri6tes  microbicides  du  serum.  Ibid.,  1S90. 
Contribution  a  l'dtude  experimental  du  charbon  symptomatique .  Revue  de  medecine, 
1891. 

2  Behring  and  Nissen.  Ueber  bakterienfiendliche  Eigenschaften  verschiedener  Blut- 
serumarten.     Ein  Beitrag  zur  Immunitatsfrage.     Zeitschrift  f.  Hygiene,  1890. 

3  Roger.  Modification  du  serum  a  la  suite  de  Perysipele.  Societe  de  biologie,  1890. 
R61e  du  semm  dans  l'attenuation  des  virus.  Revue  generate  des  sciences,  1891.  Le 
pouvoir  att6nuant  du  s6rum.     La  presse  m6dicale,  March  4,  1896. 

4  [Antimicrobic  would  be  a  more  comprehensive  expression  than  germicidal.  Trans- 
later.] 

6  Behring  and  Kitasato.  Ueber  das  Zustandekommen  der  Diphterie-Immunitat  und 
der  Tetanus-Immunitat.     Deutsche  med.  Wochenschrift,  1890. 


MECHANISM  OF  immunity  AND  OF  PREDISPOSITION.     :,:,] 

when  the  resistance  of  fche  animals  i  fcrengthened,  and  via  ver  a. 
This  clearly  shows  the  interesl  of  the  presenl    tudy. 

Natural  Immunity,  [f  the  germicidal  properties  of  the  organic 
fluids  play  a  real  role  in  the  mechanism  of  immunity  they  musl  be 

i.Ik;  more  iniirkcd  i he  more  icsistanl  the  animal.  Authors  who  have 
studied  ii:il,nr;il  iiiiinunity  have  a1  i i 1 1 1 < ■  observed  result*  contrary 
to  what  would  logically  be  anticipated.  Nuttal,  for  example, 
noticed  that  the  serum  of  the  rabbil  exerts  a  more  marked  destructive 
action  upon  the  anthrax  bacillus  than  docs  the  serum  of  the  dog. 
Hero  is  an  absolutely  misleading  fact.  Is  it  not  known  thai  the 
dog,  although  liable  to  contrad  anthrax  infection,  is  more  resistanl 
than  the  rabbit?  The  experiment  just  noted  was  of  too  greal  conse- 
quence to  be  left  uncontrolled.  We,  therefore,  took  up  the  question 
and  found  the  fact  to  be  perfectly  exact.  This  strange  fad  ifi  true 
not  only  of  anthrax,  but  also  of  symptomatic  anthrax.  The  rabbil 
is  naturally  immune  from  this  infection,  and  the  guinea-pig  i-  very 
sensitive  to  it;  and  yet  the  serum  of  the  guinea-pig  is  far  more 
germicidal  than  that  of  the  rabbit.  Experimentation  has  demon- 
strated this  fact,  and  the  conclusions  which  may  be  deduced  there- 
from deserve  to  be  discussed. 

Action  of  Serum  upon  the  Morphology  of  Microbes.  It  does  not 
suffice  to  study  the  numerical  development  of  microbes.  It  is  also 
necessary  to  investigate  what  becomes  of  their  properties  and  estab- 
lish whether  their  development  is  effected  according  to  the  normal 
type.  It  has  already  been  stated  that  the  morphology  of  the 
bacillus  anthracis  varies  with  the  serum  in  which  it  develops.  In 
the  guinea-pig  we  find  delicate  regularly  segmented  filaments  as  in 
bouillon.  In  the  rabbit  we  find  rods  either  isolated  or  united  in 
pairs.  In  the  frog,  long  chains  appear  which  are  very  slender  and 
segmented  at  variable  intervals.  These  first  facts,  which  were  con- 
firmed and  completed  by  Pane.  Pernisse,  and  Alessi,  demonstrated 
that  the  development  of  the  anthrax  bacillus  does  not  take  place  in 
a  normal  manner.  But  it  was  of  greater  importance  to  determine 
the  variations  of  virulence  under  these  different  conditions. 

Action  of  Serum  upon  Virulence.  Ogata  and  Jasuhara  have  con- 
tended that  the  anthrax  bacillus  when  sown  in  the  blood  or  the 
serum  of  the  frog,  dog,  or  white  rat  loses  its  virulence.  If.  after  two 
or  three  days,  it  is  inoculated  into  a  mouse  the  animal  resists.  The 
antiseptic  power  of  the  blood  of  the  frog  is  so  marked  that  one  drop 
suffices  to  confer  immunity  upon  a  mouse.     The  blood  of  the  dog 


558  ISFECTIOUS  DISEASES. 

and  of  the  white  rat  act  similarly,  provided  it  is  employed  in  a 
larger  dose.  The  blood  of  a  calf,  which  is  a  non-refractory  animal, 
remains  without  effect.  Sanarelli,  experimenting  with  the  serum  of 
frogs  freed  of  the  leucocytes,  likewise  noticed  that  the  bacillus  was 
attenuated  in  this  medium  within  three  or  four  days  if  it  was  sporu- 
lated,  and  more  rapidly  if  it  was  asporogenic. 

Unfortunately,  all  these  results  have  been  contradicted.  Enderlen, 
Petermann,  and  Roudenko  experimented  with  the  blood  of  dogs  or 
frogs  and  obtained  no  attenuation.  The  action  of  the  serum  is 
well  demonstrated  only  in  the  case  of  the  white  rat.  The  question 
seems  to  be  one  of  noxious  effects  exerted  upon  the  microbe  itself, 
since  the  researches  of  Metchnikoff  and  Roux  appear  to  show  that  it 
is  necessary  to  place  the  serum  and  spores  in  contact  in  order  to 
annihilate  the  pathogenic  action  of  the  latter. 

On  the  other  hand,  it  is  not  sufficient  to  study  the  chemism  of  the 
blood.  The  action  of  the  organs  must  also  be  investigated.  As  the 
microbes  retire  from  the  blood  current  into  the  viscera  and  tissues, 
in  order  again  to  invade  the  blood  at  the  end  of  life,  we  must  study 
the  modifications  which  these  microbes  undergo  in  the  depths  of 
the  economy.  Few  researches  have  been  pursued  in  this  direction, 
and  those  that  have  been  undertaken  with  another  end  by  Phisalix, 
for  example,  tend  precisely  to  demonstrate  that  microbes  find  in 
certain  tissues  favorable  conditions  which  enable  them  to  resist 
the  germicidal  action  of  the  blood.  This  result  accounts  for  the 
apparent  contraction  between  the  high  germicidal  power  of  the  fluids 
and  the  absence  of  natural  immunity.  Moreover,  in  discussing 
these  researches,  the  fact  that  the  organism  is  not  an  inert  medium 
seems  hardly  ever  to  have  been  considered.  In  fact,  the  organism 
reacts  from  the  very  start  of  the  infection,  at  the  same  time  that  it 
is  subjected  to  the  action  of  microbic  toxins.  Hence,  two  orders  of 
modifications  take  place.  Some  are  due  to  the  action  of  the  microbes, 
and  probably  reduce  the  means  of  defense;  others  depend  upon 
organic  reactions  and  strengthen  these  means  of  defense. 

In  conclusion  we  would  like  to  say  that,  in  order  to  investigate  in 
a  useful  manner  the  problem  of  natural  immunity,  we  should  pene- 
trate as  completely  as  possible  the  mechanism  of  infection  and  keep 
constantly  in  mind  that  the  various  modes  of  defense  have  only  a 
relative  and  not  an  absolute  value. 


MECHANISM  OF  IMMUNITY  AND  OF  PREDI8POSITI0 
Acquired  Immunity. 

Germicidal  Action  of  the  Serum  of  Vaccinated  Animal.s.     A     hi    already 

been  stated,  after  the  results  of  Nuttal,  which  were  nol  perfectly 
demonstrative,  we  undertook  the  study  of  the  modification*  in  the 
serum  of  vaccinated  animals.  Our  firsl  investigations,  pursued 
with  Dr.  Charrin,1  were  made  upon  the  bacillus pyocyaneus.  Blood 
taken  from  normal  and  from  vaccinated  animals  was  kepi  for  twenty- 
four  hours,  when  the  scrum  was  separated  and  pul  in  tubes,  3  cubic 
centimetres  in  each.  A  very  small  dose,  0.02  c.c.  or  0.002  c.  c.  of 
pyocyaneus  culture,  prepared  in  bouillon,  was  then  introduced  into 
the  tubes,  wliieli  were  shaken  and  subjected  to  study.  Some  experi- 
menters thought  thai  the  germicidal  action  of  the  -<Tum  under  these 
conditions  depended  simply  upon  the  facl  thai  the  culture  made  in 
bouillon  was  transferred  to  a  different  medium — i.  e.,  the  serum. 
We  therefore  often  took  our  virus  from  cultures  made  in  normal 
liquid  serum.  The  results  were  identical  in  both  instances.  In  fact, 
on  the  following  day  it  was  possible  to  clearly  see  with  the  naked  eye 
notable  differences  in  the  mode  and  intensity  of  vegetation  of  the 
microbe,  according  as  the  culture  was  made  in  normal  serum  or  in 
serum  obtained  from  vaccinated  animals.  The  normal  serum  was 
completely  opaque,  turbid,  and  of  a  bluish-green  color.  It  contained 
a  few  flocculi  which  increased  in  number  on  the  following  day.-.  <  >n 
the  other  hand,  the  serum  of  the  vaccinated  animals  became  but 
very  slightly  turbid.  The  bacilli  were  united  in  small  masses  float- 
ing in  the  fluid.  On  the  following  days  the  development  was  more 
noticeable,  and  the  differences,  although  appreciable,  were  Less 
striking. 

When,  however,  the  animal  is  well  vaccinated,  the  cultures  made  in 
its  serum  always  preserve  a  peculiar  appearance.  The  fluid  remains 
clear,  and  the  microbes  are  united  in  small  masses  which  are  scat- 
tered when  the  tube  is  shaken.  Moreover,  while  the  bacillus  gives 
a  fine  blue  color  in  normal  serum,  it  produces  no  pigment  in  the 
serum  obtained  from  vaccinated  animals;  the  culture  medium 
assumes  a  dirty  brown  hue. 

These  first  results  led  the  author  to  study  other  infections  from  this 
point  of  view,  and  he  experimented  with  the  bacillus  of  symptomatic 

1  Charrin  and  Roger.  Note  snr  le  developpement  des  microbe?  pathogdnes  dans  le 
serum  des  animaux  vaccines.     Soc.  de  biologic.  1SS9. 


560  IXFECTIO  US  DISEASES. 

anthrax.1  Guinea-pigs  were  either  vaccinated  with  the  virus  atten- 
uated according  to  the  method  of  Arloing,  Cornevin,  and  Thomas, 
or  inoculated  with  small  amounts  of  virulent  fluid  beneath  the  skin 
of  the  ear.  Four  or  five  days  after  the  last  preventive  inoculation,  in 
order  to  ascertain  their  resistance,  a  few  drops  of  symptomatic  an- 
thrax serous  exudate  mixed  with  lactic  acid  were  injected  into  the 
animals.  Those  guinea-pigs  which  resisted  were  bled  after  a  period 
varying  from  eight  to  twenty-two  days  after  the  test  inoculation,  and 
their  serum  was  inoculated  comparatively  with  the  serum  of  normal 
guinea-pigs.  The  smaller  amounts  inoculated  the  more  marked  were 
the  differences  in  development.  Thus,  when  0.08  c.c.  to  0.1  c.c. 
of  sj'mptomatic  anthrax  serous  exudate  were  mixed  with  3  c.c.  of 
serum,  it  was  noticed  on  the  following  day  that  growth  had  begun 
in  all  the  tubes,  but  was  less  pronounced  in  the  serum  obtained  from 
the  vaccinated  animals.  On  the  second  day  the  differences  were 
far  more  appreciable.  Even  the  macroscopic  appearance  showed 
that  development  was  far  more  luxuriant  in  the  normal  serum,  which 
was  completely  opaque,  and  microscopic  examination  revealed 
therein  a  far  greater  number  of  bacilli. 

A  short  time  after  our  first  investigations  the  contributions  of 
Behring,  Nissen,  and  Zasslein  appeared,  which  contributed  additional 
facts  to  those  observed  by  us.  Behring  and  Nissen  established  that 
vaccination  of  the  guinea-pig  against  MetchnikofFs  vibrio  imparts 
to  the  serum  of  this  animal  a  germicidal  power  which  is  absent  in 
the  normal  state. 

Action  of  the  Serum  upon  Morphology.  The  modifications  pre- 
sented in  the  morphology  of  the  bacillus  anthracis  have  already  been 
referred  to  in  connection  with  normal  serum.  The  influence  of  the 
serum  of  vaccinated  animals  is  still  more  definite.  Let  us  take,  for 
example,  the  cultures  of  the  bacillus  pyocyaneus.  The  microbes 
developing  in  normal  serum  present  nothing  special.  They  are 
small  rods  analogous  to  those  observed  in  artificial  culture  media 
habitually  employed  in  bacteriology.  The  appearance  is  altogether 
different  in  the  serum  of  refractory  animals.  In  the  latter  instance 
the  microbes  are  united  in  chains  of  variable  length  made  up  of  six 
to  ten  segments.  The  length  of  these  strepto-bacilli  is  less  than  that 
of  the  normal  bacilli.     The  size  of  the  segments  varies;  some  of 

1  Roger.  Nouvelles  recherches  sur  les  propridtes  microbioides  du  serum.  Societd  de 
biologie,  1890.  Contribution  a  l'dtude  experimentale  du  charbon  symptomatique. 
Revue  de  mddecine,  1891. 


MECHANISM  OF  IMMUNITY  AND  OF  PREDISPOSITION.    :,<;] 

fchem  are  extremely  short,  being  half  a  Large  a  a  normal  bacillus; 
many  attain,  and  a  few  exceed,  the  normal  length.  In  general,  .'ill 
the  segments  of  the  same  chain  are  nearly  of  the  same  dimensions. 
Some  diplo-bacilli  and  a  few  isolated  one  are  al  o  ob  erved.  The 
protoplasm  of  these  dements  does  no1  tain  a  well  a  in  the  normal 
state,  and  not  infrequently  lome  clear  patche  are  found.  Finally, 
these  elements  manifesl  a  remarkable  inclination  to  form  groups, 
and,  instead  of  swiniming  freely  like  normal  bacilli,  they  are  found 
in  small  masses,  which  accounts  for  the  clotted  appearance  of  the 
cultures.  The  differences  observed  with  symptomatic  anthrax  are 
no  less  marked  from  this  point  of  view. 

Agglutinating    Power    of    Serum.       Cultures     made   in    the  blood   of 

vaccinated  animals  presenl  a  peculiar  appearance  due  to  the  delay 
of  development  or  to  modifications  imposed  upon  certain  functions. 
At  the  same  time,  however,  an  agglomeration  of  the  figurate  element* 
may  be  observed,  which  imparts  to  the  culture  medium  a  clotted 
appearance  which  is  altogether  characteristic.  In  studying  with 
Dr.  Charrin  the  development  of  the  bacillus  pyocyaneus  in  the  serum 
of  vaccinated  rabbits  we  first  observed  the  agglutinating  power  of 
serums.  We  noted  that  the  microbes,  often  united  in  chains, 
manifested  a  strong  tendency  to  form  groups,  and,  instead  of  freely 
swimming  like  normal  bacilli,  they  formed  small  masses.  This  fact 
explains  the  appearance  of  the  cultures.  In  fact,  these  remain  clear 
and  transparent ;  the  microbes  fall  to  the  bottom  of  the  tube,  where 
they  unite  in  clots.1  Dr.  Metchnikoff2  made  similar  observations 
with  the  avicide  vibrio,  then  with  the  microbe  of  pneumonia;  but 
lie  later  recognized  that  this  agglutinating  property  does  not  belong 
to  the  sera  of  all  vaccinated  animals.  It  is  lacking,  for  instance. 
in  animals  immunized  against  the  bacillus  of  hog  cholera.  Gruber3 
took  up  the  question  and  completely  modified  the  method.  He 
introduced  a  new  and  very  simple  procedure  for  determining  whether 
or  not  a  given  serum  was  derived  from  a  vaccinated  animal.  He 
took  a  small  amount  of  culture  and  mixed  it  with  serum  upon  a  slide. 
When  the  serum  was  derived  from  a  normal  animal  the  microbes 
remained  disseminated;  when  it  was  obtained  from  a  vaccinated 

1  Charrin  and  Roger.     Xote  sur  le  developpement  des  microbes  pathog&ies  dans  le 
serum  des  animaux  vaccines.     See.  de  biologic  Nov.  23,  1SS9. 

2  Metchnikoff.    Etudes  sur  l'immunite  (4th  memoire).    Annates  de  ITnstitut  Pasteur, 
1891,  pp.  473,  474.     Etudes  sur  l'immunite  (,5th  memoireV     Ibid..  1892,  p.  29-i. 

3  Gruber.    Theorie  der  aktiven  und  passiven  ImmunitaT  gegen  Cholera.  Typhus,  und 
Verwandte  Krankheitprozesse.    Munchener  med.  Wbchensehrift,  1896,  p.  - 

36 


562  INFECTIOUS  DISEASES. 

animal  the  microbes  agglomerated  and  agglutinated.  Gruber  ob- 
served this  result  with  the  microbes  of  cholera  and  typhoid  fever 
and  noticed  that  The  phenomenon  is  clearer  the  more  intensely  the 
animal  is  immunized.  From  this  time  on  innumerable  contributions 
appeared  upon  the  question  of  agglutination.  The  chief  results 
obtained  may  be  given  in  resume  in  the  following  conclusions: 

The  agglutinating  power  often  exists  in  the  serum  of  normal 
animals.  Horse  serum  agglutinates  the  cholera  vibrio,  the  colon 
bacillus,  and  the  tj^phoid  bacillus.  Likewise  the  sera  of  most 
animals  agglutinate  the  bacilli  introduced  by  the  first  inoculation 
of  anthrax,  independently  of  any  relationship  between  the  intensity 
of  agglutination  and  the  immunity  of  the  animal.  Thus,  according 
to  Gengou,  the  serum  of  the  rat  agglutinates  in  a  dilution  of  1 :  10, 
the  serum  of  the  guinea-pig  in  1 :  20,  that  of  the  dog  in  1 :  100, 
and  that  of  man  in  1:500.  Man  is  far  more  sensitive  to  anthrax 
than  the  rat,  and  yet  his  serum  is  fifty  times  more  active.  The 
serum  of  the  guinea-pig  and  that  of  the  dog  have  an  almost  equal 
agglutinating  power,  while  the  resistance  of  these  animals  is  quite 
different. 

The  agglutinating  power  appears  not  only  in  vaccinated  animals, 
but  also  in  the  course  of  infections,  and  this  propert}',  which  is 
acquired  also  by  the  blood,  has  been  turned  to  profit  by  Widal  for 
diagnostic  purposes.  As  a  rule,  the  better  the  individual  resists  a 
disease  the  earlier  the  agglutinating  power  appears  and  the  more 
energetic  is  its  action.  The  serum  prognosis  of  P.  Courmont  is 
based  upon  this  fact. 

The  serum  acquires  agglutinating  properties  not  only  with  respect 
to  bacteria,  but  also  as  regards  more  highly  organized  plants,  as  we 
have  shown  to  be  the  case,  for  instance,  with  the  fungus  of  aphtha 
(Figs.  11  and  12,  pp.  311,  312).  Finally,  cellular  elements,  such  as 
red  blood  corpuscles,  and  organic  substances,  such  as  casein,  may 
be  agglutinated  as  well  as  microbes.  Animals  which  have  received 
blood  drawn  from  various  species  yield  a  serum  agglutinating  the 
red  blood  corpuscles  of  the  blood  which  has  been  injected  into  them. 
The  result  is  identical  when  milk  is  employed. 

The  agglutinating  reaction  is  specific.  It  is  exercised  only  upon 
the  element  against  which  the  animal  reacts.  This  fact  may  serve 
to  differentiate  microbic  species  and  even  simple  varieties. 

Attenuating  Power  of  Serum.  We  have  already  stated  that  cer- 
tain streptococci  develop  as  readily  in  the  serum  of  normal  as  in 


MECHANISM  OF  IMMUNITY  AND  OF  PBEDISPOSITIOH     .,<;.; 

that  of  vaccinated  animals,      in  pursuing  our  research! 
ni/(!(l  that  I. he  numerical  development  was    the   same,  while  the 
pathogenic,  properties,  were  quite  different.    Take,  for  in  tance 
cultures  twenty  four  hours  old,  one  prepared  in  normal  serum,  the 
other  in  that  of  a  vaccinated  animal.     It'  the  ame  amount  of  each  of 
these  cultures  is  injected  beneath  the  skin  of  the  ear  of  two  rabbits, 
the  results  are  round  to  be  quite  different.     In  some  instance 
culture  prepared  in  normal  serum  proves  highly  virulent,  and  if  a 
large  dose,  say  sixteen  drops,  is  introduced,  the  animal  diet  within 
two  or  three  days.    The  local  lesion  is  slight;  a  general  infection 
takes  place,  as  may  be  proved  by  cultivation  from  the  viscera.    The 
cultures  prepared  in  the  serum  of  the  vaccinated  animal,  under  the 
same  conditions  as  in  the  preceding,  give  rise  to  a  local  lesion,  a 
more  or  less  extensive  erysipelas;  but    the  general  state  remains 
good  and  the  animal  rapidly  recovers. 

The  streptococci  thus  acquire  different  properties  according 
they  are  developed  in  the  serum  of  normal  or  of  vaccinated  animals. 
In  both  instances  vegetation  is  similar,  but  the  microbes  derived 
from  the  serum  of  the  vaccinated  animal  lose  much  of  their  virulence 
and  become  attenuated.  This  is  an  important  fact  from  the  stand- 
point of  general  pathology. 

It  is  to  be  noted,  however,  that  the  agents  which  develop  in  the 
serum  of  animals  rendered  refractory  do  not  lose  all  of  their  patho- 
genic power:  there  is  a  reduction  but  not  abolition  of  virulence. 
This  is  not  to  be  wondered  at,  since  vaccinated  animals  develop  a 
local  lesion  when  active  microbes  are  inoculated  into  them. 

These  remarks  are  applicable  also  to  the  pneumococcus,  which 
likewise  becomes  attenuated  in  the  serum  of  refractory  animals.1 
This  result  was  confirmed  by  Arkharow.2  The  researches  of  this 
author  were  strongly  criticised  by  Metchnikoff,  in  whose  laboratory 
the  investigations  were  pursued.  Therefore,  we  shall  not  dwell  upon 
them.  We  must  mention,  however,  a  very  curious  fact  discovered 
by  Mosn}r.  According  to  this  experimenter  the  pneumococcus  lives 
longer  in  the  serum  of  a  vaccinated  than  in  that  of  a  normal  rabbit. 
This  fact  has  nothing  paradoxical  about  it.  Dr.  Mosny  himself 
remarks  that  the  microbe  is,  so  to  speak,  in  a  state  of  latent  life  in 

1  Roger.  Role  du  s<5rum  dans  l'attenuation  des  virus.  Revue  generale  des  sciences, 
June  30,  1891. 

2  Arkharow.  Gu6rison  de  l'infection  pneumonique  chez  les  lapins.  Archives  de 
medecine  exper..  July.  1892. 


564  INFECTIOUS  DISEASES. 

the  serum  of  the  vaccinated  animal.  While  the  microbe  does  not 
die,  it  does  not  develop.  It  behaves  as  in  an  unfavorable  medium. 
It  does  not  secrete  the  substances  which  arrest  its  own  vegetation. 

The  attenuating  action  of  serum  was  further  demonstrated  by  the 
experiments  of  Dr.  Courmont.  This  scientist  cultivated  the  staphy- 
lococcus aureus  in  comparative  series  in  the  sera  of  vaccinated  and 
of  normal  animals.  After  several  successive  passages  in  the  two 
media  he  transferred  the  microbes  to  bouillon,  and  these  last 
cultures  he  employed  for  inoculation.  In  this  manner  he  avoided 
introducing  therapeutic  serum.  The  virulence  was  preserved  intact 
in  the  normal  serum,  while  it  was  reduced  or  destroyed  in  the  sera 
obtained  from  animals  which  had  been  rendered  refractory.1  Anal- 
ogous researches  pursued  by  Nicolas2  proved  this  conclusion  to  be 
applicable  to  the  bacillus  of  diphtheria.  We  might  also  cite  the 
experiments  of  Denys  and  Leclef  with  streptococci  and  those  of 
Babes,  Sternberg,  Beclere,  Chambon,  and  Menard,  demonstrating 
that  the  virus  of  hydrophobia  and  that  of  vaccinia  lose  their  prop- 
erties in  contact  with  the  sera  of  refractory  animals. 

Antitoxic  Properties  of  Serums.  As  microbes  act  mostly  by  the 
toxic  substances  which  they  secrete,  it  was  natural  to  investigate 
the  action  of  serum  upon  microbic  products.  We  owe  to  Behring 
and  Kitasato  the  first  experiments  upon  this  question,  experiments 
which  oppened  a  new  route  for  therapeutics.  These  facts  are  at 
present  too  well  known  to  require  long  discussion  in  this  place. 
The  serum  of  an  animal  vaccinated  against  diphtheria  has  but  very 
slight  germicidal  power  (Nicolas),  but  it  possesses  the  far  more 
important  property  of  neutralizing  the  diphtheritic  toxin.  The 
antitoxic  power  of  the  serum  is  so  marked  that  a  guinea-pig  weighing 
400  grams  is  preserved  against  a  fatal  dose  of  toxin  by  0.008  c.c. 
of  serum.  In  other  words,  1  c.c.  of  serum  preserves  50,000  grams 
of  living  matter.  Such  is  the  strength  of  the  serum  furnished  by 
the  Pasteur  Institute. 

Tetanus  is  comparable  to  diphtheria  in  that  the  microbe  remains 
localized  at  one  point  of  the  organism  and  acts  only  by  its  toxins. 
Its  mode  of  attack  and  the  mode  of  defense  of  the  economy  are 
similar  to  what  occurs  in  diphtheria.     The  serum  of  animals  vaccin- 

1  Courmont.  Sur  les  propri6tes  bactericides  ou  microbiophiles  du  s6rum  du  lapin, 
suivant  que  cet  animale  est  vaccine  contre  le  staphylocoque  pyogene  ou  predispose  a 
cette  infection.     Archives  de  physiologie,  January,  1895. 

2  Nicolas.    Pouvoir  bactericide  du  se>um  antidiphterique.     These  de  Lyon,  1895. 


MKdllANlKM  of  IMMUNITY  AND  OF  PREDIBP08ITI0N, 

ated  against  tetanus  is  also  an  .'niiiiM.--.ic  serum.  Behring  and 
Kitasato,  to  whom  also  this  discovery  is  due,  affirm  thai  thfc  serum, 
when  injected  into  animals,  pre  erve  them  from  tetanu  .  and  may 
even  cure  the  established  disease.  They  s  serl  thai  il  u  possible 
to  save  a  mouse  which  already  manifests  the  characteristic  con- 
tractures. These  experiments,  however,  repeated  by  Tizzoni  and 
( -attain,  Vailla.nl,  and  again  by  Kitasato  himself,  gave  negative 
results  from  a  therapeutic  standpoint.  Soon  after  Roux  and  Vail- 
la.nl1  showed  that  the  serum  injected  before  inoculation  | 
the  animals.  When  introduced  simultaneously  with  the  toxin-,  or 
a  little  after,  if  diminishes  the  intensity  of  the  symptoms  and  permits 
the  development  of  only  ,a  local  tetanus,  [1  is  ab  olutery  ineffectual 
when  injected  info  animals  already  presenting  contractus 

In  a  great  number  of  infections  it  may,  perhaps,  !><•  possible  to 
prepare,  by  certain  experimental  contrivances,  cither  germicidal  or 
antitoxic  sera.  To  this  end  the  method-  of  vaccination  may  lie 
varied.  This  has  been  accomplished  by  researches  pursued  with 
regard  to  cholera  and  typhoid  fever.  Pfeiffer  obtained  a  germicidal 
serum  against  the  vibrio  of  cholera.  The  animals  which  furnished 
this  fluid  received  vibrios  killed  by  means  of  chloroform  fumes  and 
heat  and  increasing  doses  of  living  vibrios.  The  serum  acted 
against  the  disease  produced  by  intraperitoneal  inoculation  of 
cholera  bacilli,  but  it  failed  when  it  was  tried  upon  animals  inoculated 
through  the  intestine.  Even  in  cases  of  peritonitis  the  serum  acts 
only  when  it  is  injected  a  short  time  after  inoculation  and  when  the 
dose  of  virus  introduced  is  not  too  large.  Pfeiffer ,  who  has  made 
a  thorough  study  of  this  question,  has  shown  that  the  serum  should 
be  injected  half  an  hour  after  inoculation  in  order  to  succeed.  It  is 
inert  if  it  is  employed  after  an  hour  and  a  half.  The  same  author 
established  that  y¥  of  a  milligram  of  serum  suffices  to  neutralize 
2  milligrams  of  culture,  but  he  recognized  that  even  a  considerable 
amount  of  serum  does  not  protect  against  intraperitoneal  injection 
if  the  dose  of  the  culture  is  greater  than  one  platinum  loopful  per 
100  grams  of  weight  of  animal.  The  fact  is  that  when  the  culture 
is  introduced  at  the  end  of  a  certain  time  or  in  too  large  amount,  not 
only  the  microbes  introduced,  but  also  the  toxins  elaborated  within 
the  organism  or  contained  in  the  culture  must  be  taken  into  account. 
The  serum  is  only  germicidal,  it  weakens  and  kills  the  figurate 

1  Roux   and  Vaillard.      Contribution   a    l'etude   du   tetanos.      Annates   de   l'Institut 

Pasteur.  February.  1S93.  p.  65. 


566  I  -v  FECTIO  US  DISEASES. 

elements;  it  is  not  antitoxic,  namely,  it  exerts  no  action  upon  the 
poison  of  cholera.  As  a  matter  of  fact,  Pfeift'er,  Wassermann  and 
Metchnikoff  have  noted  that  vaccinated  animals  which  are  refractory 
to  virulent  inoculation  arc  as  sensitive  to  the  influence  of  toxins  as 
normal  animals,  or  even  more  sensitive 

These  results  explain  why  Pfeiffer's  methods  do  not  succeed  much 
with  man.  In  the  case  of  spontaneous  disease  the  question  is  one 
of  intoxication  rather  than  of  infection.  The  microbe  multiplies  in 
the  intestine,  but  it  is  the  toxins  absorbed  therefrom  which  act,  and 
it  is  precisely  these  toxins  that  are  uninfluenced  by  the  serum. 
Cholera  is,  therefore,  altogether  comparable  to  'diphtheria  and 
tetanus.  In  all  three  cases  the  microbes  multiply  at  a  certain  point 
in  the  organism,  and  all  the  symptoms  depend  upon  the  absorption 
of  their  toxins.  Hence,  it  was  natural  to  apply  to  cholera  the 
fundamental  principles  which  guided  Behring  in  the  study  of  diph- 
theria. This  is  what  was  undertaken  by  Ransom,  one  of  the  disciples 
of  Behring,  and  by  Drs.  Roux,  Metchnikoff  and  Taurelli-Salimbeni. 
These  authors  extracted  from  cholera  cultures  a  very  active  soluble 
poison  against  which  immunity  may  be  conferred  by  operating 
progressivelv.  A  serum  is  thus  obtained  which  proves  active  against 
choleraic  intoxication  and  meets  clinical  requirements.  It  is  thus 
possible  to  prepare  two  serums  against  cholera :  one  acting  upon  the 
living  element,  the  other  upon  the  toxin.  The  latter  is  efficacious 
against  experimental  cholera,  which  maybe  produced  in  young  rabbits 
by  causing  them  to  swallow  choleraic  cultures.  In  this,  as  in  the  case 
of  man,  the  process  is  one  of  vibrionic  intoxication.  In  the  inves- 
tigations of  Metchnikoff,  Roux,  and  Taurelli-Salimbeni,  56  per  cent, 
of  the  animals  experimented  upon  survived,  and  16  per  cent,  of  the 
controls.  In  the  same  order  may  be  mentioned  Funck's  researches 
demonstrating  that  the  poison  contained  in  the  protoplasm  of  the 
typhoid  bacillus  gives  rise  to  the  appearance  of  germicidal  substances 
in  animals.  The  serum  is  very  efficacious  against  infection  by  the 
living  microbes,  but  exerts  no  influence  upon  the  typhoid  toxins. 
Chantemesse,  on  the  other  hand,  by  utilizing  a  special  toxin,  pre- 
pared an  antitoxic  serum. 

It  would  seem  at  first  sight  that  nothing  is  easier  of  explanation 
than  the  mode  of  action  of  antitoxic  serums.  The  idea  suggesting 
itself  immediately — and  such  was  Behring's  idea — is  to  assume  that 
the  antitoxin  neutralizes  the  toxin  as  an  acid  neutralizes  a  base. 
The  serum  is  supposed  to  contain  a  true  antidote  destroying  the 


MECHANISM  OF  IMMUNITY  AND  OF  PREDISPOSITION.    r,i;7 

poison.  Hence  the  Hume  loxmicidej  which  is  sometime  given  to  it. 
Behring's  conception  was  combated  by  Buchner,  Ehrlich,  !.'■ 
Vaillard,  Calmette,  Bouchard,  etc.  [f  a  quantity  A  of  serum  neutral- 
izes  a  quantity  B  of  toxin  in  such  a  manner  a  to  render  the  mixture 
inoffensive,  2A  should  neutralize  2B,  3A  should  neutralize  3B,  and  •> 
on.  Such  is  not  the  case,  however.  When  the  quantitie  ol  erum 
and  of  toxin  are  increased  progressively  a  momenl  arrives  when  the 
toxin  acts.  Any  amoun.1  of  serum  may  then  I"-  employed,  bul 
there  will  no  longer  be  any  antitoxic  effect.  Thus,  an  inoffensive 
mixture  in  the  dose  of  I  cubic  centimetre  will  prove  fatal  it  2  or  3 
cubic  centimetres  are  injected.  We  hardly  need  dwell  upon  this 
fact  which,  from  a  practical  standpoint,  is  of  greal  consequi 
since  it  explains  certain  failures  of  serum  therapy.  It  is  also  im- 
portant from  a  theoretical  standpoint,  since  it  proves  thai  the 
process  is  not  one  of  neutralization  in  the  chemical  sense  of  the  term. 
Another  objection  was  formulated  by  Buchner.  This  author  pre- 
pared a  mixture  of  tetanus  toxin  and  antitetanic  serum.  He  in- 
jected it  into  a  mouse  without  giving  rise  to  any  symptoms ;  but  he 
discovered  that  the  mixture  was  still  active  as  regards  the  guinea-pig. 

When  inoffensive  doses  of  the  mixture  of  toxin  and  serum  are 
introduced  the  animal  may  be  rendered  sensitive  to  the  neutralized 
poison  by  modifying  its  resistance  by  means  of  certain  microbes. 
Thus  Roux  and  Vaillard  showed  that  guinea-pigs  vaccinated  against 
the  vibrio  of  Massouah  take  tetanus  when  they  are  injected  with  a 
mixture  of  toxin  and  serum,  which  mixture  is  inoffensive  for  normal 
guinea-pigs.  On  the  other  hand,  a  normal  guinea-pig  was  inoculated 
with  the  same  mixture.  No  symptom  was  produced,  but  when,  a 
few  days  later,  the  soluble  products  or  various  microbes  such  as  the 
Kiel  bacillus  or  colon  bacillus  was  injected,  tetanus  was  declared. 
The  poison  was,  therefore,  always  present.  A  modification  of  the 
organism  sufficed  to  enable  it  to  act. 

Calmette  obtained  analogous  results  by  means  of  venoms.  He 
prepared  a  mixture  of  venom  and  serum,  and  noted  that  this  mixture 
was  inoffensive.  He  heated  it  for  five  minutes  at  154.5°  F.  (6S°  C). 
At  this  temperature  the  action  of  the  serum  was  destroyed,  while 
that  of  the  venom  remained  intact.  He  then  injected  the  mixture, 
which  was  inactive  a  little  while  before,  and  this  time  the  animal 
died.  There  was,  therefore,  no  destruction  of  poison,  but  simply  a 
simultaneous  presence  in  the  fluid  of  two  substances  with  antagon- 
istic action. 


568  IMECTIOUS  DISEASES. 

The  conclusion  is  evident :  Since  the  antitoxin  does  not  act  upon 
the  toxin,  it  therefore  influences  the  organism  itself  in  such  a  manner 
as  to  enable  the  cells  to  resist  the  action  of  the  poison  or,  perhaps, 
not  to  be  penetrated  by  it  at  all. 

Passage  of  Active  Substances  into  the  Secretions,  and  Notably  into 
the  Milk.  The  active  substances  which  are  found  in  the  blood 
of  vaccinated  animals  possess  the  property  of  passing  into  certain 
secretions,  natural  fluids,  and  transudations.  This  was  demon- 
strated by  Stern,1  Prudden,2  and  Gottstein3  by  studying  the  serous 
fluid  of  vesicatories,  of  ascites,  pleurisy,  hydrocele,  and  the  amniotic 
fluid.  Unlike  the  microbic  toxins,  which  are  rapidly  eliminated  by 
the  urine,  as  was  shown  by  Prof.  Bouchard,  the  active  substances 
of  the  serum  do  not  seem  to  pass  into  the  urine.  When  an  animal 
is  vaccinated  its  urine  possesses  no  therapeutic  property.  Such 
may  not  be  the  case  when  therapeutic  serums  are  injected,  since  an 
observation  reported  by  Vagedes  shows  that  tetanus  antitoxin  passes 
into  the  renal  secretion.  It  is  detected  therein  for  eleven  days.  It 
is  difficult,  however,  to  draw  a  conclusion  from  this  case,  since  it 
was  that  of  a  patient  afflicted  with  tetanus,  and  it  is  not  known  what 
role  is  to  be  attributed  to  infection  and  what  to  serum  therapy. 

The  only  secretion  which  is  important  from  a  practical  standpoint 
is  the  milk.  Since  Brieger  and  Ehrlich4  called  attention  to  this  fact 
a  great  number  of  experimenters  have  recognized  that  the  milk 
contains  therapeutic  substances,  but  in  quite  small  amounts.  Ehr- 
lich showed  the  immunizing  power  of  milk  of  animals  vaccinated 
against  abrin  and  ricin.  Klemperer  and  Levy  established  the  same 
fact  as  regards  the  typhoid  bacillus;  but  the  milk  of  an  immunized 
goat  was  ten  times  less  active  than  the  serum  of  the  same  animal. 
Particular  researches  in  this  connection  have  been  pursued  with 
regard  to  cholera  and  diphtheria.  The  works  of  Popoff,  Ketscher, 
and  Klemperer  demonstrated  the  passage  of  anti cholerine  into  milk. 
Popoff5  showed  that  the  active  principle  is  found  in  the  serum  of 

1  Stern.     Ueber  die  Wirkung  des  menschlichen  Blutes  und  anderer  Korpersfliissig- 
keiten  auf  patogene  Mikroorganismen.     Zeitschrift  f .  klin.  Medicin,  1890,  Bd.  xviii. 

2  Prudden.  On  the  Germicidal  Action  of  Blood  Serum  and  Other  Blood  Fluids.  Med- 
ical Record,  1890. 

3  Gottstein.  Zusammenf .  Uebersicht  uber  die  bakterienvernichtende  Eigenschaft  des 
Blutserum.     Therap.  Monatshefte,  1891. 

4  Brieger  and  Ehrlich.  Ueber  die  Uebertragung  von  Immunitat  durch  Milch.  Deut. 
med.  Wochenschrift,  1892. 

5  Popoff.     Uebertragung  der  Immunitat  gegen  Cholera  mittels  der  Milch  einer  vac- 


MECHANISM  OF  IMMUNITY  AND  OF  PREDISP08ITI0N.    $09 

the  milk  and  was  destroyed  by  boiling.  KetBcher  Bhowed  thai  ih<- 
milk  acts  when  it,  is  injected  beneath  the  skin.  When  it  if  introduced 
by  the  alimentary  canal  it  is  inert.  The  experimenl  were  made 
upon  vibrionic  peritonitis,  and,  therefore,  it  v.;i  the  germicidal 
stanee  that  passed  ini.D  the  milk.  In  order  to  tudy  the  antitoxic 
substance,  wo  must  consider  ihe  researches  pursued  with  diphtheria. 

Wassermann  and  Ehrlich1  employed  goats'  milk.  At  the  begin- 
ning of  vaccinal  ion  5  c.c.  were  required  to  neutralize  the  toxin. 
Later,  0.1  c.c.  sufficed.  The  serum  was  twentytimes  more  active. 
The  authors  remark,  however,  that  a  goat  yield-  in  one  month  a 
litre  and  a  half  (a  quart  and  a  half)  of  serum,  or  30  litres  of  milk. 
It  would,  therefore,  be  advantageous  to  employ  the  latter  -eejetion 
if  it  could  be  concentrated  so  as  to  obtain  the  active  substance 
in  a  small  volume.  This  is  what  Wassermanri  tried  to  do.  After 
coagulating  the  milk  by  means  of  lab-ferment,  he  precipitated  the 
active  substance  by  sulphate  of  ammonia.  The  precipitate,  dried 
in  vacuo  and  again  dissolved,  proved  highly  effective;  0.125  c.c. 
of  the  fluid  thus  obtained  sufficed  to  neutralize  0.9  c.c.  of  the  diph- 
theritic poison. 

The  employment  of  milk  may,  therefore,  be  of  service  in  thera- 
peutics. The  same  is  true  of  eggs.  In  fact,  Klemperer's  researches 
show  that  anticholerine  is  found  in  the  yelk  of  the  egg  of  hens 
vaccinated  against  the  vibrio.  According  to  Sclavo,  the  white  of 
the  egg  contains  the  diphtheritic  antitoxin.  Here,  therefore,  is  a 
new  field  open  to  therapeutics.  It  is  not  impossible  that  some  day, 
when  active  substances  will  be  prepared  in  a  state  of  purity,  milk 
and  eggs  of  vaccinated  animals  will  replace  the  serum. 

Germicidal  Properties  of  Tissues.  Do  the  tissues,  under  the  in- 
fluence of  vaccination,  undergo  modifications  analogous  to  those 
of  the  fluids?  Such  is  the  question  which  we  endeavored  to  elucidate 
after  our  first  investigations  on  the  germicidal  properties  of  serum. 
The  problem  was  not  new.  It  had  long  been  laid  down  and  taken 
up  by  various  experimenters,  and  almost  always  received  a  negative 
answer.  The  majority  of  experimenters  admit,  as  a  dogma,  that 
microbes  develop  equally  well  in  all  tissues  deprived  of  life,  no  matter 

cinierten  Kuh.     Vratch,   1S93.  No.  10  (Anal.  Centralblatt    f.  Bakt.,   1895,  Bd.  xvii. 
p.  166). 

1  Wassermann.  Ueber  Konzentrierung  der  Diptherie-Antitosdne  aus  der  Milch  im- 
muuisierte  Tliiere.  Zeitschrift  f.  Hygiene.  Bd.  xvii.  p.  233.  Ehrlich  and  Wassermann. 
Ueber  die  Gewinnung  der  Diptherie-Antitoxine  aus  Blutserum  und  Milch  immunisierte 
Thieve.      Ibid.,  p.  239. 


570  INFECTIOUS  DISEASES. 

whether  they  arc  derived  from  animals  enjoying  natural  or  acquired 
immunity,  or  not.  Unfortunately,  the  contributions  thus  far  pub- 
lished arc  open  to  criticism.  Bouillon  prepared  with  the  muscles 
of  animals  has  always  been  employed.  It  is  to  be  noted  that  heat 
destroys  the  germicidal  properties  of  the  fluids,  and  it  must  evidently 
act  in  the  Same  manner  upon  the  tissues.  Hence,  it  was  necessary 
to  practice  cultivation  without  any  previous  preparation.  The 
experiment  thus  conceived  was  not  as  simple  as  might  seem  at  first 
sight.  The  majority  of  aerobic  microbes  do  not  develop  in  the 
interior  of  dead  tissues  where  oxygen  is  lacking.  It  is  difficult, 
if  not  impossible,  to  appreciate  with  accuracy  the  intensity  of  vege- 
tation inside  an  organ  or  a  tissue  and  to  recognize  whether  or  not 
development  is  similar  in  animals  sensitive  to  the  disease  and  in  those 
that  are  naturally  or  artificially  immune. 

All  these  difficulties  disappear  when  an  anaerobic  agent  is  em- 
ployed, which  lives  free  from  air,  and  the  multiplication  of  which 
may  be  appreciated  with  some  accuracy  by  the  amount  of  gas 
liberated.  These  various  conditions  are  fulfilled  by  the  bacillus  of 
symptomatic  anthrax.  Hence,  we  have  chosen  this  microbe  for 
studying  the  problem  laid  before  us.  We  first  investigated  the 
behavior  of  this  bacillus  when  inoculated  into  tissues  separated  from 
the  body  and  derived  from  normal,  viz.,  non-vaccinated  animals. 

We  operated  in  the  following  manner:  The  animal,  rabbit,  or 
guinea-pig  being  killed  by  hemorrhage,  we  detached,  with  every 
antiseptic  precaution,  the  four  extremities.  Then,  by  means  of  a 
Pravaz  syringe,  we  injected  into  each  limb  from  1  to  5  drops  of  the 
serous  fluid  drawn  from  an  anthrax  tumor  of  a  guinea-pig.  We  thus 
made  four  injections  with  one  animal.  Immediately  after  the  virus 
was  injected  the  four  extremities  were  placed  in  sterilized  vessels 
and  put  in  an  incubator  with  a  temperature  of  93.2°  F.  (34°  C).  At 
the  end  of  fifteen  or  seventeen  hours  it  may  readily  be  recognized 
by  palpation  that  the  tissues  of  the  rabbit  as  well  as  those  of  the 
guinea-pig  are  infiltrated  with  gas.  This  emphysema  is  really  due 
to  the  development  of  symptomatic  anthrax  and  not  to  putrefaction, 
since  it  is  not  produced  in  non-infected  limbs  prepared  in  the  same 
manner.  We  are  therefore  led  to  conclude  that  the  tissues  of  the 
rabbit  and  guinea-pig  present,  after  death,  excellent  culture  media 
for  the  bacillus  of  symptomatic  anthrax.  There  is  no  relation 
between  the  natural  immunity  of  the  animals  and  the  resistance 
which  their  tissues,  deprived  of  life,  may  oppose  to  the  multipli- 


MECHANISM  OF  IMMUNITY  AND  OF  PBEDI8P08ITI0N.    :,l  \ 

cation  of  the  microbe.  This  rei  nil  maj  I"-  compared  to  thai  ob- 
served in  serum,  [t  seems,  however,  lea  paradoxical,  since  the 
muscles  of  the  guinea-pig  are  invaded  as  readily  by  the  microbic 
agent  as  those  of  the  rabbit.  H  is  no  le  int<  r<  ting  to  note  that, 
after  death,  the  tissues  of  a  naturally  immune  animal  no  longer 
opposes  the  development  of  a  pathogenic  agenl  which  could  nol 
develop  during  life. 

Let  us  now  consider  whal  occurs  in  vaccinated  guinea  pig  and 
in  rabbits  the  natural  immunity  of  which  ha  been  reinforced  by 
means  of  preventive  inoculations.  The  animal*  were  treated  in 
the  same  manner  as  in  I  lie  preceding  experiments:  the  four  limbs 
worn  separated  from  the  body  and  inoculated  al  the  same  time  and 
in  the  same  manner  as  the  limbs  of  normal  animals.  At  the  end 
of  fifteen  hours  the  I  issues  of  (lie  latter  are  infiltrated  with  gas; 
those  of  the  vaccinated  animals  do  not  contain  any.  Sometime 
later  it  is  found  thai  emphysema  develops  in  the  vaccinated  limbs. 
Crepitation  is  appreciable  at  the  end  of  twenty-four  or  twenty-eight 
hours;  but  the  amount  of  gas  is  very  small  and  in  now  ise  comparable 
to  that  infiltrating  the  tissues  of  the  normal  limbs.  After  thirty-six 
or  forty  hours  the  differences  are  still  quite  notable.  Although  the 
tissues  of  the  vaccinated  limbs  give  the  sensation  of  emphysema,  it 
is  easy  to  see  that  the  tissues  of  the  normal  animals  are  so  swollen 
that  even  a  slight  touch  will  reveal  the  characteristic  crepitation. 

In  some  of  our  experiments  we  took  the  precaution  to  irrigate 
the  circulatory  system  in  order  to  remove  all  trace  of  blood  before 
practising  inoculation.  For  this  purpose,  the  animal  having  been 
killed  by  hemorrhage,  we  first  detached  one  of  the  thighs.  After 
ligating  the  vessels  opened  during  this  operation,  we  incised  the 
abdominal  wall  and  injected  through  a  canula  introduced  into  the 
aorta  a  7 :  1000  sterilized  salt  solution,  which  came  out  through 
the  inferior  vena  cava.  The  amount  of  fluid  thus  employed  was 
360  c.c.  The  remaining  thigh,  which  had  been  thus  washed,  was 
then  detached,  and  the  two  limbs  were  inoculated  in  the  same 
manner  and  placed  in  the  incubator.  We  found  that  the  washing 
of  the  circulatory  system  did  not  modify  the  results.  It  neither 
restricted  nor  favored  the  development  of  symptomatic  anthrax 
and  in  nowise  modified  the  differences  which  are  observed  according 
as  the  tissues  experimented  upon  were  those  of  normal  or  of  vac- 
cinated animals. 

The  procedure  employed  in  these  researches  is  open  to  some 


572  INFECTIOUS  DISEASES. 

criticism.  It  serves  to  elucidate  only  one  of  the  phenomena  accom- 
panying microbic  development.  It  may  be  objected  that  the  bacilli 
develop  in  the  tissues  of  vaccinated  animals  and  that  only  one  of 
their  functions  is  suppressed.  Such  an  objection  is  not  in  harmony 
with  the  facts  known  of  the  biology  of  anaerobics;  at  any  rate,  the 
objection  is  of  little  value.  In  fact,  it  matters  little  whether  the 
vegetation  or  the  function  of  the  microbe  is  checked.  It  suffices 
for  us  to  establish  that  development  differs  according  as  the  tissues 
employed  are  those  of  vaccinated  or  of  normal  animals.  This  result, 
which  seems  to  be  undeniable,  proves  that  a  chemical  modification 
takes  place,  no  matter  whether  this  modification  occurs  in  the 
muscles,  the  connective  tissue,  or  the  interstitial  fluids.  The  only 
legitimate  conclusion  to  be  drawn  from  our  investigations — and  this 
is  precisely  the  answer  to  the  question  which  we  proposed  to  solve — 
is  that  the  bacillus  of  symptomatic  anthrax  develops  with  difficulty 
in  the  tissues  of  vaccinated  animals. 

This  conclusion  is  in  harmony  with  that  arrived  at  by  Bitter, 
who  found  that  extracts  of  tissues  possess  germicidal  properties. 
Domssen  also  learned  that  the  extract  of  the  tissues  of  rabbits  vac- 
cinated against  the  pneumococcus  possesses  vaccinating  properties. 

A  very  skilful  experiment  of  Voswinkel  tends  to  prove  that  the 
tissues  of  certain  naturally  refractory  animals  are  likewise  germicidal. 
This  author  experimented  upon  frogs  the  blood  of  which  he  re- 
placed by  sterilized  salt  water.  He  then  injected  into  them  1  c.c. 
or  2  c.c.  of  anthrax  culture.  The  microbes  introduced  soon 
perished,  while  those  which  were  kept  at  the  same  temperature  in 
salt  water  preserved  their  vitality.  On  studying  the  phenomena 
more  closely,  Voswinkel  recognized  that  while  some  bacilli  were 
incorporated  by  some  remaining  leucocytes,  the  majority  disinte- 
grated outside  them. 

Modifications  of  the  Serum  in  Animals  Predisposed  to  Infections. 
After  studying  the  chemical  modifications  occurring  in  the  organism 
when  its  resistance  is  increased  we  were  naturally  led  to  investigate 
what  happened  under  opposite  conditions.  As  is  known,  a  great 
number  of  procedures  may  be  employed  to  increase  the  sensitiveness 
of  animals  to  infection.  This  may  be  realized,  for  example,  by 
injecting  into  them  the  soluble  products  of  streptococci,  viz.,  cultures 
filtered  through  a  porcelain  bougie  and  not  heated.  The  animals 
thus  treated,  when  later  inoculated,  die  more  rapidly  than  normal 
animals.     Under  these  conditions  the  serum  is  far  less  germicidal 


MECHANISM  OF  IMMUNITY  AND  OF  PREDISPOSITIO         :,-,:', 

than   under  normal  conditions,     Ai    tiniei    the  difference 
marked   that  fifteen  or  twenty  hours  after  inoculation  of  th< 
microscopic  examination  sho^    innumerable  germs  in  the  cultures 
prepared  with  the  serum  of  the  weakened  animals,  while  in  those  cul- 
tures made  with  normal  serum  only  one  <>r  i  wo  chains  are  sieen  in  each 
microscopic  field.    The  differences  disappear  soon  after,  and,  ai  the 
end  of  two  or  three  days,  the  two  cultures  are  numerically  similar, 
but  not  equally  virulent.     Animals  which  receive  the  culture  derived 
from  the  sera  of  predisposed  animals  die  before  those  which  re< 
a  culture  developed  in  normal  serum. 

The  results  which  we  obtained  with   the  serum  of  predisp 
animals  thus  represent  the  counterpari  of  those  furnished  by  the 
study  of  the  sera  of  vaccinated  animals,     in  the  latter  case  the 
microbe  is  attenuated;  while  in  the  former  instance  h  is  exalted,  or 
rather  it  seems  to  be  exalted;  for  some  experiments,  which  ari 
incomplete,  tend  to  show  thai  the  sera  of  predisposed  animals 
not  upon  the  microbe,  but  upon  the  inoculated  animal  whose  r< 
ance  it  reduces. 

The  streptococcus  is  not  the  only  microbe  that  secret*  s  predispos- 
ing substances.  Like  substances  are  secreted  by  the  sta]  ihyl<  icoccus. 
In  this  case  also  the  serum,  as  was  shown  by  Courmont,  lose.-  its 
germicidal  properties.  To  use  the  author's  expression,  it  becomes 
bacteriophilic. 

Analogous  modifications  are  observed  under  various  circumstances. 
At  times  diminution  of  resistance  seems  to  depend  upon  a  diminution 
of  the  alkalinity  of  the  blood.  This  hypothesis  explains  how  over- 
exertion weakens  the  resistance  of  the  white  rat  to  anthrax  infection. 
In  fact  it  is  known  that  the  resistance  of  this  animal  depends  upon 
the  high  alkalinity  of  its  blood.  The  analyses  of  Drouin  demon- 
strated that  this  alkalinity  diminishes  in  rats  when  they  are  foi 
to  do  violent  muscular  work.  likewise,  according  to  Zagari  and 
Innocenti,  the  alkalinity  of  the  blood  is  weakened  in  animals  sub- 
jected to  the  action  of  chloral,  tartaric  acid,  and  alcohol,  and  in 
heated  frogs,  and  in  pigeons  subjected  to  fasting.  In  all  cases  there 
is  a  remarkable  parallelism  between  the  diminution  in  the  alkalinity 
of  the  blood  and  the  reduction  of  resistance.  The  influence  of 
fasting  was  particularly  demonstrated  by  the  experiments  of  Canalis 
and  Morpurgo.1     After  four  or  six  days  of  fasting  the  pigeon  lost 

1  Canalis  and  Morpurgo.     Intorno  all'  influenza  del  digiuno  sulla  disposwone  alle- 
malattie  infettive.     Roma.  L890. 


574  IXFECTIOUS  DISEASES. 

its  immunity  against  anthrax.  At  this  time  it  possessed  very  little, 
if  any,  germicidal  power.  In  only  one  experiment  the  blood  re- 
mained germicidal,  and  this  time  the  animal  preserved  its  immunity. 
Gaertner1  likewise  observed  that  the  staphylococcus  vegetates  more 
luxuriantly  in  the  blood  of  rabbits  whose  resistance  to  infection  was 
reduced  by  .means  of  deficient  alimentation  and  repeated  bleeding. 
On  the  other  hand,  if  bleeding  is  only  once  practised,  the  resistance 
is  not  diminished,  even  when  the  loss  of  blood  is  great.  In  accord- 
ance with  this  result,  the  blood  remains  germicidal,  as  was  shown 
by  Bakunin  and  Boccardi.2 

Modifications  of  the  Serum  in  the  Course  of  Acute  Diseases.  It 
might  be  assumed  that  the  germicidal  properties  of  the  serum 
increase  when  the  individual  recovers,  and  that  they  diminish  when 
the  patient  dies.  In  reality  the  phenomena  are  far  more  complex. 
Even  in  fatal  cases  the  organism  generally  reacts.  Therefore,  the 
germicidal  properties  may  increase.  From  the  very  start  of  our 
researches  we  noted  with  astonishment  that  the  serum  of  animals 
succumbing  to  an  infection  is  at  times  as  strongly  germicidal  as  the 
serum  of  vaccinated  animals  and  likewise  hinders  certain  functions. 
The  animal  dies  because  the  protective  substances  are  insufficient 
in  quantity  or  have  appeared  too  late.  They  may  nevertheless 
exert  a  harmful  action  upon  the  microbes  that  have  invaded  the 
organism.  Hence,  cultures  obtained  from  individuals  dead  of 
certain  infections  may  be  destitute  of  virulence.  This  occurs  con- 
stantly in  cases  of  streptococcic  infections.  The  organism  succeeds 
in  attenuating  the  microbe,  but  the  latter  has  time  to  secrete  toxins 
which  injure  the  principal  organs  and  render  recovery  impossible. 
Hence,  it  is  not  rare  to  see  death  occur  after  destruction  of  microbes. 
We  therefore  remark  that  in  the  course  of  infections  two  different 
processes  go  on  simultaneous^.  Microbic  products  are  elaborated 
which  tend  to  diminish  the  germicidal  properties,  while  the  reactions 
of  the  organism  tend  to  increase  them.  We  may  readily  conceive 
the  variability  of  results  according  as  one  or  the  other  process 
predominates. 

In  certain  instances  the  role  of  reduction  of  germicidal  power  in 
the  course  of  infections  has  been  appreciated.     By  producing  local 

1  Gaertner.  Beitrag  zur  Aufklarung  des  Wesens  des  sog.  Praedisposition.  Ziegler's 
Beitrage  zur  patholog.  Anat.,  1890. 

2  Bakunin  and  Boccardi.  Ricerche  su  la  proprieta  battericida  del  sangue  in  diversi 
stati  dell'  organismo.     La  Riforma  medica,  1891,  t.  iii.  p.  445. 


MECHANISM  OF  IMMUNITY  AND  OF  PRED1   PO   XTI01       57fi 

lesions,  which  subsequently  became  generalized,  Bastin  found  thai 
invasion  of  fche  organism  is  preceded  by  a  diminution  of  the  germ- 
icidal power.  The  degree  of  thii  diminution  i  in  dired  ratio  to  the 
intensity  of  the  infection.  On  the  other  hand,  in  two  women  suffer- 
ing from  local  abscesses,  I'nsiin  found  thai  ac  regard  the  taphylo- 
coccus  the  blood  was  more  germicidal  than  normal,  and  this  fad 
accounted  for  the  Localization  of  the  lesion.  Analogous  to  these 
results  are  those  obtained  by  Kiouka,  Szekely  and  Szana,  Km-'-. 
and  Pansini.  Experimenting  with  the  staphylococcus,  bacillus 
anthracis,  and  pneumococcus,  these  authors  noticed  thai  the  germ- 
icidal power  diminished  and  disappeared  when  infection  became 
generalized — /.  <•.,  when  the  microbes  passed  in  large  numbers  into 
the  blood.  On  the  contrary,  in  typhoid  cases  the  germicidal  prop- 
erties persist  until  death  and  the  microbes  do  nol  invade  the  Mood 
(Kiouka). 

Importance  and  Significance  of  Modifications  ns  I  i  i  ids.  In 
view  of  the  facts  reported,  it  may  be  concluded  that  there  i-  a 
remarkable  parallelism  between  the  variation  of  the  organic  n 
ance  and  the  action  of  the  blood  upon  bacteria.  When  the  resistance 
is  increased  the  protective  role  of  the  blood  is  more  marked,  and  vice 
versa.  These  correlations  are  at  times  so  perfect  that,  as  regards 
the  pneumococcus,  for  example,  the  serum  culture  gives  the  measure 
of  receptivity  (Kruse  and  Pansini).  The  results  are  not  comparable, 
however,  unless  the  experiment  is  pursued  upon  the  same  animal 
species. 

These  facts  have  not,  however,  sufficed  to  convince  all  scieiv 
Some  objections  have  been  raised  against  the  so-called  humoral 
theory  which  we  must  briefly  consider.  We  shall  not  dwell  upon 
erroneous  criticisms.  It  is  quite  certain,  for  example,  that  germ- 
icidal power  does  not  depend  upon  a  change  of  medium — i.  c.  upon 
transference  from  bouillon  to  serum.,  On  the  contrary,  the  germ- 
icidal action  is  unmodified  when  a  germ  grown  in  the  serum  of  a 
normal  animal  is  inoculated  into  the  serum  obtained  from  a  vaccin- 
ated one. 

The  important  objection  is  the  argument  that  the  germicidal 
properties  do  not  exist  in  the  blood  circulating  in  the  bloodvess  3. 
They  appear  when  the  blood  is  in  an  abnormal  condition,  when  it  has 
been  coagulated  or  defibrinated.  This  is.  so  to  speak,  an  artificial 
property  developing  after  death,  due.  perhaps,  to  disintegration  of 
leucocytes  and  to  diffusion  of  substances  contained  in  them. 


5  7 6  IXFECTIO  US  DISEASES. 

It  may  be  replied,  in  the  first  place,  that  it  is  quite  strange  that  the 
germicidal,  attenuating,  or  antitoxic  power  of  the  serum  varies  with 
the  degree  of  resistance,  that  it  is  increased  when  the  animals  are 
vaccinated,  and  diminished  when  their  immunity  is  weakened.  In 
this  maimer  the  blood  of  vaccinated  animals  acquires  a  new  power 
which  is  in.  a  latent  state  in  the  organism,  and  becomes  manifest  as 
soon  as  this  fluid  leaves  the  vessels.  This  power  would  thus  act  when 
it  is  useless.  A  good  many  facts,  however,  tend  to  prove  that  the 
protective  action  is  real  and  is  readily  exercised  during  life.  The 
passage  of  active  substances  into  natural  effusions,  such  as  the 
serous  fluid  produced  by  vesicatories,  ascites,  pleuritic,  hydrocele, 
and  the  amniotic  fluids  and  their  presence  in  milk,  cannot  be  ex- 
plained otherwise  than  by  the  admission  that  the  blood  contains  a 
diffusible  soluble  principle. 

Moreover,  there  are  a  few  experiments  which  prove,  by  other 
methods,  that  the  protective  action  really  exists  during  life.  This 
may  be  demonstrated  by  protecting  the  microbes  against  the  phag- 
ocytes by  means  of  parchment  bags,  by  injecting  germs  beneath  the 
skin,  and  after  a  few  minutes  studying  the  modifications  presented 
by  them.  De  Giaxa  and  Guarnieri  introduced  the  microbe  into  a 
segment  of  artery  tied  at  the  two  ends.  The  modifications  were 
found  to  be  the  same  as  outside  the  organism.  Drs.  Denys  and 
Leclef  injected  streptococci  beneath  the  skin  of  the  ear  of  normal 
and  of  vaccinated  rabbits.  In  the  former  they  noted  that  the 
microbes  rapidly  developed  and  that  the  leucocytes  were  not  late  in 
appearing  at  the  spot;  but,  while  some  of  these  fulfilled  their  phago- 
cytic action,  the  majority  remained  passive  and  did  not  attack  the 
invaders.  In  the  vaccinated  animal,  on  the  contrary,  the  microbes 
rapidly  disappeared.  The  number  of  leucocytes  making  their  appear- 
ance at  the  spot  was  the  same  as  in  the  former  instance,  but  the 
microbes  were  weakened  by  the  serum,  and  the  leucocytes  succeeded 
in  devouring  them  within  a  few  hours.  These  original  and  accurate 
experiments  elucidate  the  various  phases  of  the  struggle  between 
the  microbe  and  the  organism.  Whether  the  animal  is  vaccinated 
or  not,  the  leucocytes  migrate  with  the  same  facility ;  but  this  afflux 
of  cells  is  not  necessarily  followed  by  phagocytosis.  The  microbes 
are  more  readily  picked  up  because  they  had  been  previously  affected 
by  the  fluids — i.  e.,  by  the  chemical  substances  dissolved  in  the 
blood  serum.  Another  conclusion  to  be  drawn  from  these  researches 
is  that  the  active  substance  in  the  serum  of  vaccinated  animals  can 


MECHANISM  OF  IMMUNITY  AND  OF  PREDI8P08ITI0N.    577 

no  longer  be  considered  as  a  stimulinf  exciting  the  phagocytic  pi 
•of  the  cells,     [t  seems  rather  thai  the   erum  aci    upon  the  microbe 
by  weakening  its  vitality  or  by  neutralizing  the  uoxiou     ub  tancee 

secreted  by  if. 

Nature  and  Origin  of  the  Various  Active  Substances  Contained 
in  the  Serum.  We  have  indicated  the  principal  modifications 
presented  by  the  blood  in  the  course  or  in  consequence  of  infections. 
Wo  must  now  consider  (he  relationship  exi  ting  between  the  various 
■substances  the  effects  of  which  have  been  alluded  to.  We  musi 
ask  what  is  the  significance  and  I  he  cause  of  germicidal,  agglutinat- 
ing, and  antitoxic  actions. 

It  may  first  be  stated  thai  certain  normal  animals  furnish  agglu- 
tinating serums,  others  germicidal  serums.  Vaccination  does  not, 
therefore,  produce  a  new  property.  On  the  contrary,  it  increases 
or  modifies  an  already  existing  property.  The  study  of  serums 
obtained  from  normal  and  vaccinated  animals  demonstrates,  on  the 
other  hand,  that  there  is  no  constant  relationship  between  the 
agglutinating  and  germicidal  powers.  Thus,  the  serum  of  the  nor- 
mal dog  agglutinates  the  bacilli  introduced  by  first  inoculation  of 
anthrax,  but  it  does  not  destroy  them.  Moreover,  numerous  obser- 
vations demonstrate  that  the  agglutinated  microbes  are  not  dead 
and  that,  under  certain  conditions,  they  are  capable  of  development. 
The  two  properties  may  be  separated.  Heating  to  131°  F.  (55°  C.) 
abolishes  the  germicidal  power,  but  modifies  the  agglutinating  power 
very  little,  if  at  all.  The  two  substances  may  also  be  separated  by 
dialysis.  The  germicidal  substances  pass  through  the  collodion  sac : 
the  agglutinating  substances  do  not. 

By  investigating  the  relationship  existing  between  the  germicidal 
and  the  therapeutic  powers  of  serums,  Frankel  and  Sobemheim 
found  that  serum  heated  to  140°  F.  (60°  C.)  loses  its  germicidal 
action,  but  preserves  its  preventive  power.  It  still  confers  im- 
munity upon  guinea-pigs  into  which  it  is  injected.  Bordet  took  up 
the  experiment  and  demonstrated  that,  by  adding  a  certain  amount 
of  normal  serum  to  the  heated  preventive  serum,  the  germicidal 
power  reappeared.  This  highly  interesting  result  shows  that  the 
serum  of  a  vaccinated  animal  acts  by  means  of  two  substances. 
One  is  a  specific  substance  resisting  a  temperature  of  141°  F.  (60°  C.) ; 
the  other,  present  in  normal  serum,  is  a  common  substance  which 
is  incapable  of  destroj-ing  bacteria  except  when  the  latter  have  been 
influenced  by  the  specific  substance.     In  other  words,  vaccination 

37 


578  INFECTIOUS  DISEASES. 

causes  the  appearance  of  a  substance  which  renders  the  microbe 
sensitive  to  the  alexin  contained  in  every  serum. 

Continuing  the  study  of  these  facts,  Bordet  demonstrated  that 
this  specific  substance  unites  with  the  pathogenic  agent  against 
which  the  animal  is  immunized.  Under  its  influence  the  microbes 
lose  theh  motility  and,  in  the  second  phase,  they  agglutinate.  After 
the  remarkable  contributions  of  Bordet,  agglutination  must  be  con- 
sidered a  physical  phenomenon  comparable  to  coagulation.  It 
results  from  a  change  in  the  relations  of  molecular  adhesion  between 
the  bodies  of  the  cells  and  the  fluid  containing  them.  In  order  for 
this  agglutination  to  be  produced  it  is  necessary  for  the  substance 
to  possess  a  certain  mineral  composition,  and,  notably,  contain 
sodium  chloride.  When  the  agglutinating  serum  is  placed  in  contact 
with  microbes  suspended  in  distilled  water  the  latter  remain  separate ; 
when  sodium  chloride  is  added  they  come  together  and  agglutinate. 
These  results  are  observed  not  only  outside  but  also  within  the 
organism.  Frankel  and  Sobernheim  injected  into  guinea-pigs  the 
serum  of  a  vaccinated  animal  after  heating  the  serum  to  158°  F. 
(70°  C).  The}7",  therefore,  introduced  a  non-germicidal  serum. 
The  serum  of  the  animal  thus  treated  acquired  the  germicidal  power 
which  had  disappeared  from  the  injected  serum.  This  fact  is  im- 
portant, since  it  demonstrates  that  we  must  not,  as  is  often  done, 
believe  the  properties  of  the  serum  to  be  absolutely  unlike  those  of 
the  plasma.  Furthermore,  recent  researches  by  Rehm,  Camus,  and 
Pagniez  seem  to  demonstrate  that  the  alexins  are  not  artificial 
products  and  that  they  pre-exist  in  the  circulating  blood. 

The  origin  of  the  specific  substance  is  completely  unknown.  All 
that  is  known  about  it  is  that  it  is  not  produced  or  contained  in  the 
leucocytes. 

The  investigations  of  Deutsch  demonstrated  that  the  liver,  kidneys,, 
and  suprarenal  capsules  contain  very  little  agglutinin.  The  spleen, 
the  lymphatic  glands,  and  the  bone-marrow  contain  more,  but  the 
amount  is  still  less  than  that  found  in  the  blood.  On  the  other  hand, 
the  lungs  contain  more  of  it,  but  these  organs  also  contain  it  nor- 
mally. It  would  be  interesting  to  learn  whether  the  lungs  play  an 
important  role  in  the  formation  of  this  substance.  As  to  the  alexins, 
the  researches  of  Denys,  Havet,  and  Hahn  have  conclusively  shown 
that  they  proceed  from  the  leucocytes.  But  there  is  another 
problem  connected  with  this  subject.  Do  the  white  blood  cor- 
puscles alone  elaborate  alexin?    Cannot  other  cells  also  participate 


MECHANISM  OF  IMMUNITY  AND  OF  PM  DJ    PO   1 1  in;      579 

in  this  function?    Kven  supposing  thai  the  leucocytes  are  th< 
producers  of  the  germicidal  substance,  i    i1  to  !"•  pre  umed  thai 
they  retain  it  in  their  interior  and  thai  il    erve    only  to  d< 
the  microbes  ingested  by  the  leucocyte  ?    When  it  1    encountered 
in  various  fluids,  is  it  to  be  suppoi  ed,  following  Metchnikoflf'a  school, 
that  alexin  diffuses  only  after  the  destruction  of  leucocytes?    Or  is 
it  to  be  admitted,  as  does  Buchner,  thai  it  \t  constantly  given  off 
as  a  secretion?    This  is  the  only  poinl  upon  which  the  adherenta 
of  the  so-called  humoral  and  cellular  doctrines  of  immunity  are  not 
agreed.     The  question  is  undoubtedly  of  greal   importance  from  a 
theoretical  standpoint.     If  the  germicidal  substances   remain  en- 
closed within  the  leucocytes,  phagocytosis  retains  ite  importance. 
If  they  diffuse,  the  phenomena  of  extracellular  digestion  become 
predominant  and  the  modifications  of  the  humore  assume  an  im- 
portant position.    It  is  well  to  remark,  moreover,  thai  even  suppos- 
ing that  the  germicidal  substances  do  not   leave  the  leucocyt 
and  this  hypothesis  seems  to  us  contradicted  by  certain  facts  above 
reported,  since  the  sensibilizing  substance  is  not  of  leucocytic  origin 
—the  modification  of  the  fluids  explains  all  acquired  immunity. 
The  phagocyte  is  capable  of  digesting  only  those  microbes  which 
have  been  acted  upon  by  the  specific  substance,  viz.,  that  substance 
which  is  found  in  fluids  modified  by  infection.     Thus,  owing  to  the 
fine  contributions  of  Bordet,  we  return  to  the  conception  of  acquired 
immunity  as  it  was  understood  years  ago  by  Bouchard  and  his 
disciples. 


CHAPTER    XX. 

CONGENITAL  INFECTIONS  AND  HEREDITY. 

Passage  of  Microbes  through  the  Placenta.  The  Law  of  Brauell-Davaine.  Experi- 
ments upon  Anthrax  Infection.  Transmissibility  of  Some  Human  Infections. 
Congenital  Variola.  Peculiar  Characters  of  This  Clinical  Form.  Course  of  Tem- 
perature in  Congenital  Variola.  Its  Analogy  with  Experimental  Variola.  Trans- 
mission of  Chronic  Infections:  Leprosy,  Syphilis,  and  Tuberculosis.  Congenital 
Dystrophies  of  Infectious  Origin:  Role  of  Syphilis  and  of  Tuberculosis.  Trans- 
mission of  Immunity.  Laws  of  Colles  and  of  Profeta.  Role  of  Father  and  <>f 
Mother  in  the  Transmission  of  Immunity.     Conclusions. 

The  history  of  heredity  of  infectious  diseases1  must  be  considered 
from  a  triple  standpoint:  transmission  of  the  living  microbe  from 
parents  to  progeny;  transmission  of  modifications  in  fluids  and  cells, 
namely,  chemical  or  dynamic  changes  occurring  in  the  organism  of 
the  parents  in  the  course  or  in  consequence  of  infections ;  influence  of 
diseases  of  the  parents  upon  the  development  of  the  child  during  and 
after  intrauterine  life. 

Passage  of  Microbes  through  the  Placenta. 

Let  us  first  consider  the  simplest  question:  the  contamination  of 
the  fetus  by  living  germs.  Clinical  observation  has  long  demon- 
strated the  reality  of  fetal  infections;  it  will  suffice  to  cite  variola 
and  syphilis.  There  are,  however,  other  infections  in  which  the  prob- 
lem is  more  complex  and  more  difficult  of  solution.  The  explanation 
of  inherited  tuberculosis  has  given  rise  to  numerous  contradictory 
works  upon  the  subject.  Some  writers  have  asserted  the  possibility 
of  fetal  contamination  by  the  father  or  by  the  mother;  others,  pur- 
suing the  discussion  on  similar  lines  to  those  which  apply  to  syphilis, 
have  described  cases  of  early  or  of  tardy  heredity,  while  still  a  third 
school  has  totally  rejected  the  idea  of  direct  transmission  and  held 
tubercular  heredity  to  be  nothing  more  than  a  congenital  predispo- 
sition to  contract  the  disease.  According  to  the  last-mentioned 
hypothesis,  it  is  not  the  bacillus  but  the  soil  favorable  to  its  develop- 
ment that  is  transmitted. 

1  Roger.  L'h6r6dite  dans  les  maladies  infectieuses.  Gazette  hebdomadaire,  October 
11,  18,  and  25,  1889. 


CONGENITAL  INFECTIONS  AND  HEREDITY.  :,-\ 

Experimental  pathology  has  taken  up  the  problem,  and  the  number 
of  works  bearing  upon  this  question  i  very  considerable.  Prom  ;> 
general  point  of  view,  we  may  firsl  cite  the  magnificenl  researches 

upon  discuses  of  (he  silkworm.    Ii  i    known  thai  these  worm 
liable  to  two  main  infections:  pebrinand  Bacherie.    Pebrin  i    fci 
mitted  from  generation  to  generation  through  theegge  which  contain 
the  pathogenic  agent.    The  lal  ter  is  incorporated  with  the  egg  inside 

the  female  chrysalid,  .- 1 1 1 < I  heroines  .'in  integral  pari  '<r  the  embryo 
and  the  worm  evolved  From  it.  The  male  doei  no1  transmil  the 
disease,  but  it  may  exercise  upon  the  progeny  a  harmful  influence 

as  expressed  by  weakness  of  I  Ik-  worm  and  the  inferior  quality  of  its 
cocoon.  In  flic  case  of  llaclierie  flic  agenl  of  the  disease  resides  in 
the  intestine  and  does  not  invade  the  eggs.    The  worms  issuing  from 

contaminated  animals  do  not  have  the  disease,  bu1  they  are  weak 
and  almost  certainly  predestined  to  become  victims  of  the  contagion. 
It  is  the  morbid  predisposition  that  is  transmitted.  Do  we  not  find 
in  the  history  of  these  affections  of  the  silkworm  the  counterpart  of 
what  occurs  in  syphilitic  and  tuberculous  infections  of  more  highly 
developed  organisms? 

Intraplacental  Transmission  of  Anthrax.  It  was  with  anthrax, 
the  experimental  disease  par  excellence,  that  the  first  attempt  was 
made  to  solve  the  problem  whether  or  not  infectious  germs  may  pass 
through  the  placenta  and  invai  le  the  fetus.  Brauell,  in  1858,  reported 
four  experiments  upon  a  colt  and  three  sheep.  Microscopic  exam- 
ination showed  no  bacilli  in  the  fetus,  and  inoculation  into  animals 
gave  rise  to  no  symptoms.  Davaine  added  one,  and  Bollinger,  in 
1876,  reported  three  more  negative  results.  The  question  then 
seemed  to  be  settled  and  the  law  of  Brauell-Davaine.that  the  placenta 
was  a  perfect  filter,  was  admitted.  A  first  opposition  was  raised  hv 
Arloing,  Cornevin,  and  Thomas,  who  were  convinced  that  sympto- 
matic anthrax  was  transmitted  from  the  mother  to  the  fetus.  In 
1882  Straus  and  Chamberland  published  a  few  facts  which  seemed 
to  confirm  Branch's  law:  but, by  pursuing  their  studies. these  authors 
later  recognized  that  such  transmission  was  at  times  possible.  They 
experimented  upon  twenty  guinea-pigs ;  microscopic  examination  of 
the  blood,  liver,  and  the  spleen  revealed  no  bacilli.  The  fetus  pre- 
sented no  alterations  whatever,  and  the  blood  did  not  offer  the  agglu- 
tinating property  which  is  observed  in  animals  dead  from  anthrax. 
But  the  result  was  altogether  different  when  the  authors  employed 
another  method — i.  c,  when  thev  resorted  to  cultures  and  intoxica- 


582  INFECTIOUS  DISEASES. 

tions.  They  thus  obtained  several  positive  results,  especially  by  cul- 
i  ivation,  since  inoculations  quite  often  failed.  On  examining  twenty- 
six  fetuses  they  detected  the  bacillus  anthracis  in  fourteen  of  them. 
Their  investigations  established  the  fact  that  in  certain  rare  cases 
anthrax  is  not  transmitted  to  any  of  the  fetuses  of  the  same  litter; 
in  other  instances  the  disease  attacks  all  of  the  fetuses;  in  most  cases 
it  affects  only  some  of  them.  At  all  events  the  number  of  bacilli 
penetrating  the  fetal  organism  is  extremely  small;  this  fact  accounts 
for  the  negative  results  obtained  by  the  first  investigators.  The  ex- 
periments of  Straus  and  Chamberland  gave  rise  to  a  great  number  of 
researches  which  confirmed  the  conclusions  of  the  two  French  scien- 
tists. Such  were  those  of  Perroncity,  Koubassoff,  Birch-Hirschfeld, 
Rosenblath,  and  Latis. 

There  are  also  some  interesting  observations  as  regards  man. 
Marchand  reports  the  case  of  a  woman  who  died  from  anthrax  a  few 
hours  after  confinement,  and  her  child  succumbed  to  the  same  infec- 
tion four  days  later.  There  were  numerous  bacilli  in  the  placenta 
and  ulcerations  in  the  chorionic  villi.  Paltauf  reports  a  case  in 
which  bacilli  were  found  in  the  lungs  of  a  fetus  of  five  months  from 
a  woman  suffering  from  anthrax.  In  two  cases  observed  by  Eppinger 
and  in  another  by  Morisani  the  results  were  negative.  It  may  be 
concluded  from  all  these  experiments  and  from  the  observations  thus 
far  published  that  the  bacillus  of  anthrax  may  pass  through  the 
placenta ;  but  the  fact  is  far  from  being  constant,  and  the  number  of 
bacilli  invading  the  fetus  is  always  very  limited.  We  now  appreciate 
why  the  bacilli  were  not  found  by  microscopic  examination  except 
in  a  few  cases. 

It  is  quite  difficult  to  determine  the  frequency  of  intraplacental 
transmission  of  anthrax.  At  any  rate,  in  this  case,  as  in  all  other 
cases  of  this  kind,  statistics  can  give  no  more  than  illusive  results 
and  present  no  interest  from  a  scientific  standpoint.  The  bacillus 
anthracis  passes  into  the  fetus  in  a  variable  manner  because  the 
conditions  which  seem  apparently  identical  are  in  reality  dissimilar ; 
the  animals  react  differently,  according  to  a  multitude  of  circum- 
stances which  are  often  very  difficult  to  explain.  In  other  words,  the 
experiment  is  modified  by  various  conditions  which  favor  or  hinder 
this  passage.  The  experimenter,  therefore, instead  of  discussing  the 
frequency  of  the  phenomenon,  should  endeavor  to  learn  why  and 
especially  how  it  is  produced.  We  are,  therefore,  indebted  to  Dr. 
Malvoz,  who  attempted  to  explain  the  mechanism  by  which  the  intra- 


CONGENITAL  INFECTIONS  AND  HEREDITY. 

placental  passage  of  anthrax  takes  place.    The  research*     of  this 
author  show  that  the  indispen  able  condition  re  ide   intheexi  tence 
of  placental  alterations.    Hence,  i1  i   intelligible  why  non  pathogenic 
microbes,  such  as  the  bacillus  prodigio  u  .  are  incapable  <>f  pa 
the  barrier.    The  same  is  true  of  inerl  iufa  tai  a        ich  ■■>    sulphate 
of  barium  and   [ndia  ink;  it'  other  bodies  can  pa      i1   i    owing  to 
lesions  produced  by  solid  or  resisting  substances.    I'  may,  ther< 
be  said  in  conclusion  that  no  passage  of  figurate  elements  occurs 
without  alteration  in  the  placenta.    Moreover,  Malvoz  remarks  thai 
the  bacilb'  are  transmitted  to  the  fetus  more  easily  in  the  guim 
than  in  the  ral  >l  >il ,  .-i ,  fad  which  is  <  xplained  by  the  greater  frequency 
of  placenta]  alterations  in  the  former  of  these  animals. 

Those  very  interesting  experiments  give  no  final  solution  of  the 
problem;  they  only  Ie:ul  lo  (he  in acs ligation  of  the  conditions  which 
favor  placental  alterations  which,  under  apparently  identical  condi- 
tions, give  rise  to  different  lesions.  The  problem  is  undoubtedly  a 
difficult  one;  but  it  is  a  satisfaction  to  have  its  terms  laid  down  and 
to  see  how  successive  discoveries  tiring  out  new  complications  in  the 
question. 

Intraplacental  Transmission  of  Human  Infections.  We  have  thus 
far  considered  microbes  especially  attacking  lower  animals;  we  now 
come  to  those  which  are  of  greater  importance  for  human  pathology. 

The  study  of  the  streptococcus  is  extremely  interesting,  owing  to 
the  fact  that  it  is  the  most  frequent  agent  of  puerperal  septicemia. 
Lorrain  had  already  observed  peritonitis  in  children  born  of  septic 
women.  The  observations  of  Simone,  Lebedeff,  Hanot.  Luzet,  Haus- 
halter,  and  others  demonstrate  the  intraplacental  transmission  of  the 
streptococcus.  A  case  observed  by  the  author  seems  to  demonstrate 
that  the  death  of  the  fetus  does  not  occur  in  every  case.  A  woman 
suffering  from  measles  gave  birth  to  a  child  of  eight  months  weighing 
four  and  one-quarter  pounds.  The  author  obtained  a  pure  culture 
of  streptococcus  with  the  blood  of  the  umbilical  cord:  the  child  had 
an  attack  of  icterus,  but  it  soon  recovered,  and  a  month  later,  when 
it  left  the  ward,  it  weighed  five  and  one-quarter  pounds.  It  had  not 
only  withstood  the  streptococcic  infection  revealed  by  the  culture, 
but  even  gained  a  pound  in  weight. 

As  has  ahead}7  been  stated,  the  child  does  not  seem  to  be  infected 
in  the  course  of  erysipelas.  In  twelve  cases  women  suffering  from 
erysipelas  were  delivered  at  full  term,  and  all  the  children  survived 
without  presenting  any  notable  disorder. 


584  IXFECTIO  US  DISEASES. 

The  existence  of  congenital  pneumonia  has  long  been  admitted, 
Grisolle  asserts  that  this  affection  is  not  rare  in  the  newborn,  and 
that  it  ends  fatalty  within  a  few  hours,  when  autopsy  will  reveal 
disseminated  foci  and  even  abscesses  in  the  lung.  The  last-men- 
tioned condition  renders  somewhat  doubtful  the  nature  of  the  disease 
transmitted  and  suggests  rather  the  idea  of  pj^emia  with  pulmonary 
involvements.  Netter,  who  pursued  interesting  researches  on  this- 
subject,  reported,  in  1886,  the  transmission  of  the  pneumococcus  in 
guinea-pigs ;  of  four  fetuses  the  issue  of  a  contaminated  mother,  two 
contained  the  microbe.  Analogous  facts  have  been  observed  by  Foa. 
and  Uffreduzzi  in  the  rabbit  and  Ortmann  in  the  guinea-pig.  The 
transmission  of  the  pneumococcus  is,  therefore,  possible  in  animals 
as  well  as  in  the  human  species.  Thorner  reported  a  case  in  which 
the  mother  was  confined  at  full  term  after  defervescence  of  pneu- 
monia; the  child  succumbed  in  thirty-six  hours,  and  the  autopsy 
revealed  hepatization  of  the  lower  left  lobe,  and  the  microscopic  exam- 
ination detected  the  pneumococcus.  The  most  complete  observation 
is  Netter's.  In  this  case  the  child  succumbed  after  five  days.  This 
lapse  of  time  might  lead  to  the  suspicion  that  perhaps  a  contamination 
had  taken  place  after  birth.  However  that  may  be,  the  lesions  were 
very  marked,  consisting  in  hepatization  of  the  right  apex  with  pleu- 
ritic and  pericardial  pseudomembranes  and  fibrinopurulent  exudates 
in  the  meninges.  This  was,  therefore,  a  case  of  infectious  pneumonia 
the  nature  of  which  was  demonstrated  by  bacteriological  examina- 
tion; the  generalization  of  the  lesion  is  readily  accounted  for  by  the 
direct  entrance  of  the  morbid  germs  into  the  blood.  Bacteriological 
investigations  may  likewise  detect  the  pneumococcus  in  fetuses  from 
mothers  suffering  from  any  one  of  the  various  affections  which  may 
be  produced  by  this  microbe.  Netter  cites  an  observation  of  Hecker 
concerning  a  woman  who  died  of  a  suppurative  meningitis ;  the  child, 
delivered  by  a  Cesarean  operation,  died  at  the  end  of  thirty-four 
hours,  and  the  autopsy  showed  left  lobar  pneumonia  with  pleuritic 
and  pericardial  effusions.  The  author  had  the  opportunity  to  observe 
a  pregnant  woman  suffering  from  measles  and  intense  bronchitis. 
She  gave  birth  to  a  child  of  eight  months  which  succumbed  a  few 
hours  after  birth.  Pine  cultures  of  pneumococcus  were  obtained 
from  the  blood  and  organs  of  the  fetus,  and  the  same  microbe  was 
found  in  large  numbers  in  the  expectorations  of  the  mother.  Here 
is  an  example  of  an  infection  which,  in  spite  of  its  benign  character 
and  its  apparently  exclusive  location  in  the  bronchi,  had  really 


CONGENITAL  INFECTIONS  AND  HEREDITY. 

infected  the  maternal  organism,  since  the  pathogenic  agent   had 

invaded  the  fetus  and  mused  its  death.  Friedlander'i  microbe  al  o 
may,  according  to  Nefter,  be  bran  imitted  to  the  fetu  ,  On  the  other 
hand,  Foaand  Rattone  believe  thai  it  favori  abortion,  bu1  doe  doI 
pass  to  the  placenta.  In  pregnanl  guinea  pigs  inoculated  through 
the  peritoneum,  abortion  occurred  within  thirt}  is  or  forty-eighl 
hours,  and  no  microbes  were  found  either  in  the  fetut  or  in  the 
placenta. 

While  speaking  of  lnmian  diseases  we  may  mention  typhoid  f< 
since  the  transmission  of  this  Infection  to  the  fetus  reems  to  be  well 
demonstrated  by  recent  observations.  Eberth's  bacillus,  penetrat- 
ing directly  into  the  blood,  kills  the  fetus  by  inducing  septicemia. 
This  is  a  new  illustration  of  symptomatic  variations  which  may  be 
observed  according  to  the  age  of  the  subjects  or  the  mode  of  entrance 
of  the  virus. 

With  reference  to  cholera,  we  may  cite  an  observation  of  Tizzoni 
and  Cattani  upon  a  woman  suffering  from  this  infection  who  - 
birth  to  a  fetus  of  five  months.  In  this  case,  as  in  the  majority  of 
other  diseases,  microscopic  examination  did  not  detect  the  presence 
of  any  microbe,  while  cultivation  enabled  the  experimenters  to  find 
the  comma  bacillus. 

Recurrent  fever  has  also  been  known  to  be  transmitted  to  the 
fetus,  and  in  this  instance  Spitz  was  able  to  discover  Obermei<i  '< 
spirilla  in  the  embryo.  It  must  also  be  remembered  that  the  trans- 
mission of  intermittent  fever  to  the  fetus  seems  to  have  been  estab- 
lished by  some  of  the  older  observers.  Stokes  recorded  the  case  of 
a  pregnant  woman  suffering  from  tertian  paroxysms  whose  child  had 
convulsions  on  the  days  when  the  mother  enjoyed  apyrexia.  Pities 
and  Aubanais  have  seen  malarial  mothers  giving  birth  to  children 
which  presented  hypertrophy  of  the  spleen  and  febrile  paroxysn  - 
the  same  daj^s  and  hours  as  their  mothers.  Schurig,  Hoffman,  and 
Russel  have  published  similar  observations.  Among  the  infectious 
diseases  the  pathogenic  agents  of  which  are  unknown  or  little  known 
we  may  cite  acute  articular  rheumatism  (Follack  and  Schaeffer)  and 
especially  hydrophobia,  which  are  sometimes  transmitted  to  the 
fetus. 

The  transmission  of  the  hydrophobic  virus  was  first  demonstrated 
by  clinical  observation.  Lafosse  saw  a  rabid  cow  give  birth  to  a 
calf  which  presented  the  first  symptoms  of  hydrophobia  three  days 
after  birth.    Perroncito  and  Carita  have  recently  studied  this  ques- 


586  INFECTIOUS  DISEASES. 

tion  from  an  experimental  standpoint:  A  rabbit  which  had  been 
inoculated  with  hydrophobia  gave  birth  to  a  litter  of  four.  One  day- 
prior  to  the  appearance  of  paralytic  symptoms  the  spinal  cord  of 
two  of  the  young  ones  was  inoculated  into  two  guinea-pigs,  one  of 
which  developed  hydrophobia,  the  other  resisted.  The  transmission 
of  the  virus  -of  hydrophobia,  however,  seems  to  occur  but  exception- 
ally. Moreover,  it  is  known  that  the  blood  has  nearly  always  been 
found  free  from  infecting  properties,  and,  on  the  other  hand,  it  is 
well  established  that  only  those  microbes  that  can  invade  the  blood 
are  capable  of  penetrating  the  placenta.  Several  experiments  were 
made  in  the  Pasteur  Institute  with  negative  results.  The  medulla 
of  eight  of  the  young  born  of  hydrophobic  animals  were  inoculated, 
and  none  of  these  medullas  proved  virulent.  It  may,  of  course,  be 
objected  that  perhaps  in  the  fetus  the  virus  does  not  reside  in  the 
nervous  centres.  This  objection  is  refuted  by  Zagarri's  experiments. 
This  author  operated  upon  fourteen  pregnant  females  inoculated  with 
the  fixed  virus;  thirty-two  young  ones  were  thus  obtained  for  the 
experiments.  The  nervous  centres,  liver,  sometimes  the  entire  fetus 
were  used,  but  the  inoculations  practised  upon  rabbits  and  guinea- 
pigs  produced  no  results. 

Transmission  of  Eruptive  Fevers. 

Vogel,  Heine,  Rilliet  and  Barthez  published  several  cases  of  con- 
genital measles,  the  mother  having  been  attacked  before  confinement. 
We  know  also  of  a  few  cases  of  congenital  scarlatina  recorded  by 
more  or  less  ancient  authors — Baillou,  Ferrario,  Portier,  and  others. 
Such  facts  must  be  very  rare,  since  the  author  has  never  observed  a 
case  of  congenital  measles  or  scarlatina. 

Congenital  Variola.  Variola  is  the  disease  which  has  furnished 
the  greatest  number  of  observations  of  congenital  infection.  The 
facts  observed  are  the  more  valuable,  as  the  child  on  coming  into 
the  world  sometimes  presents  characteristic  lesions  and  there  can, 
therefore,  be  no  doubt  as  to  the  nature  of  the  disease.  A  few  cases 
possess  the  certainty  of  an  experiment  and  have  served  purposes  of 
inoculation  with  positive  results  (Gervis,  Jenner).  Hereditary  vari- 
ola is  particularly  frequent  when  the  mother  contracts  the  disease 
toward  the  end  of  gestation.  As  in  the  case  of  anthrax,  in  twin 
births  the  contamination  of  only  one  of  the  infants  is  a  possible  event. 
In  the  observation  of  Kaltenbach,  a  woman  suffering  from  variola 
was  delivered  of  three  children;  two  of  them  had  pustules,  the  third 


CONGENITAL  INFECTIONS  AND  HEREDITY.  587 

did  not.  No!,  infrequent  ly  the  variola  of  the  fetu  i  more  recenl  than 
that  of  the  mother;  the  latter  may  be  convale  cenl  and  give  birth 

to  a  child  bearing  fully  developed  pu  i'il<  .  Iii  :i  t'v.  ca  e  the  fetus 
h;iH  contracted  the  disease  while  the  mother  remained  exempt. 
Finally,  even  when  there  is  no  tran  mi  ion,  properly  o  called,  and 
the  fetus  presents  no  alteration  its  organism  may  have  been  pro- 
foundly modified  under  the  influence  of  the  maternal  disease,  and 
thus  it  is  born  vaccinated,  baving  acquired  immunity  in  the  ut 

Such  are  the  results  admitted  by  all  classical  authoriti 
observations  am  not  in  harmony  with  the  descripl  ion  thus  far  given. 
During  the  epidemic  of  1901,  eighteen  women  wire  confined  in  OUT 
hospital.  The  children  never  presented  al  birth  the  slightest  erup- 
tion. One  of  them  manifested  no  disturbance  whatever,  and  flour- 
ished. The  others  appeared  a,l  first  to  be  exempt,  but  a  more  atten- 
tive observation  revealed  a  certain  number  of  disorders,  showing 
that,  notwithstanding  the  absence  of  easily  appreciable  symptoms, 
these  children  were  all  variolizcd.1  The  germ  of  variola  had  con- 
stantly passed  through  the  placenta.  Infection  was  produced 
whether  the  maternal  variola  was  discrete  and  curable,  as  was  the 
case  in  six  of  them,  or  fatal,  as  occurred  in  the  other  patients.  The 
passage  of  the  germs  is  rapidly  effected.  One  of  the  children  was 
born  a  day  before  the  mother  was  taken  sick;  another  a  few  hours 
after  invasion;  three  others  a  day  after.  In  eleven  cases  confinement 
occurred  on  the  second  or  the  third  day  of  the  disease,  that  is,  a 
little  before  the  eruption  or  coincidently  with  it,  and  once  eight  days 
after.  Three  children  were  born  at  seven  months,  the  others  at  full 
term.  At  first  they  seemed  to  be  normal,  and  nothing  would  have 
suggested  a  congenital  infection  if  their  temperatures  had  not  been 
taken.  The  information  thus  obtained  was  unexpected.  All  these 
children  were  hypothermic;  in  no  case  did  the  thermometer,  intro- 
duced into  the  rectum,  rise  to  98.6°  F.  (37°  C);  in  most  cases  it 
remained  below  96.8°  F.  (36°  C).  In  some  instances  it  fell  rapidly 
to  87.8°,  86°,  and  even  82.4°  F.  (31°,  30°,  and  2S°  C).  This  hypo- 
thermia seemed  to  express  a  profound  infection  which  had  over- 
whelmed the  organism.  If  the  child  is  sufficiently  resistant  and 
capable  of  reacting,  the  temperature  rises  and  may  reach  normal  or 
even  104°  F.  (40°  C).  In  the  latter  case  there  are  also  observed 
cutaneous  manifestations  expressing  an  effort  of  the  organism  to 

1  Roger.    Variole  des  nouveau-iies.    Soc.  mod.  des  hopitaux.  March  29,  1901. 


588 


IXFECTIOUS  DISEASES. 


seven  months 


eject  the  morbid  element.    According  as  these  reactions  appear  or 
are  absent  the  observations  may  be  divided  into  two  groups. 

The  first  group  contains  six  cases  in  which  the  children  suc- 
cumbed without  presenting  any  symptom  indicative  of  variola. 
A  woman  suffering  from  hemorrhagic  variola  to  which  she  suc- 
cumbed on  the  eighth  day  had,  on  the  day  prior  to  the  invasion, 
given  birth  to  a  child  at  full  term  weighing  six  and  one-half  pounds. 
At  the  time  when  the  child  was  admitted  to  our  wards,  that  is  three 
days  after  birth,  it  presented  a  rectal  temperature  of  96  F.  (35.6  C.) . 
It  was  suffering  from  a  slight  icterus,  which  became  aggravated  the 
following  day,  when  the  child  succumbed  with  a  temperature  of 
96.4°  F.  (35.8°  C).  The  second  case  was  that  of  a  child  born  at 
The  mother  had  a  discrete  variola  from  which  she 
easily  recovered.  The  child  was  born  on  the  third 
day  of  the  mother's  disease,  the  day  following  the 
eruption.  Two  days  after  birth  it  developed  a 
slight  icterus.  Its  temperature  fell  on  the  fifth  day 
to  86°  F.  (30°  C).  Then,  as  if  a  reaction  was  com- 
ing, it  rose  rapidly,  and  in  two  days  reached  98.6°  F. 
(37°  C),  when  the  child  died.  (Fig.  40.)  The  other 
cases  were  analogous.  Death  may  supervene  very 
rapidly  ;  thus  a  child  born  at  seven  months  of  a 
mother  suffering  from  hemorrhagic  variola,  to  which 
she  succumbed  sixteen  hours  later,  lived  only  five 
hours.  Its  rectal  temperature,  taken  ten  minutes 
after  birth,  was  87.8°  F.  (31°  C). 

In  such  cases  the  symptomatology  consists  in  a 
subnormal  temperature  and  icterus.  It  may,  there- 
fore, be  questioned  whether  we  are  not  in  the  pres- 
ence of  weak  children  and  whether  we  have  any 
right  to  speak  of  variolar  infection.  The  analysis 
of  the  second  group  of  cases  will  enable  us  to  answer 
this  question.  We  shall  first  cite  the  case  of  a  child 
born  at  full  term.  The  mother  developed  on  the 
day  of  her  confinement  the  first  symptoms  of  a  hemorrhagic  vari- 
ola, to  which  she  succumbed  on  the  eighth  day.  The  temperature 
of  the  child  at  first  oscillated  around  96.8°  F.  (36°  C.) ;  it  rose  on 
the  ninth  day  to  100.7°  F.  (38.2°  C),  to  fall  again  the  next  day  to 
98.6°  F.  (37°  C).  On  that  day  a  scarlatiniform  erythema  made  its 
appearance  and  covered  the  whole  body,  being  more  marked  on  the 


Fig 

40 

5      6      7 

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Congenital  variola. 


CONGENITAL  INFECTIONS  AND  HEREDITY. 


face.    The  child  seemed  to  I"'  in  a  satisfactory  condition,  l>ut  it 
suddenly  died  in  syncope  the  following  night.    In  the  other  ob  er- 
vations  the  evolution  was  more  complete;  il  terminated  in  the  d 
opment  of  a  characteristic  eruption  which  in  most  ca  i  quite 

discrete,  and  sometimes  remained  al  the  papulou     phase.     This 
occurred  in  four  cases. 

The  temperature  may  rise  a  high  at  in  the  adult.  A  child  had 
104°  F.  (40°  C.)  on  the  thirteenth  day  coincidenl  with  the  appearance 
of  a  few  papules  on  the  body.    Death  Bupervened  the  following 

In  several  cases  I  he  eruption  Hue  remained  al  the  stage  of  papules, 
either  because;  the  evolution  was  suddenly  interrupted  by  death  or 
because  the  elements  were  rapidly  dried.  Purulenl  transformation 
is  possible,  however.    A  well-developed  child  was  born  al  full  term; 


Fio.  41. 

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Congenital  variola. 

the  mother  had  suffered  for  three  days  from  hemorrhagic  variola,  to 
which  she  succumbed  six  days  later.  The  rectal  temperature  of  the 
child,  which  was  95°  F.  (35°  C),  rose  on  the  following  days.  At  the 
same  time  icterus  developed.  Then  a  febrile  movement  occurred  on 
the  tenth  day,  during  which  the  temperature  reached  104°  F.  (40°  C). 
A  crop  of  about  fifteen  papules  appeared  upon  the  back.  face,  and 
hands.  The  child  emaciated  and  refused  the  bottle.  The  evolution 
of  the  eruption  continued.  The  fever,  as  in  the  variola  of  the  adult, 
fell  to  rise  again,  and  its  renewal  coincided  with  a  purulent  transfor- 
mation of  the  eruption.  This  fever  of  suppuration  was  suddenly 
interrupted  on  the  twentieth  day  by  a  final  hypothermia.  (Fig.  42. 
Here  is  a  case  in  which  the  evolution  is  similar  to  that  in  the  adult. 
It  differs,   however,   in   two   important   characteristics — an  initial 


590 


/ NFE(  •Tinl TS  DISEASES. 


hypothermia  and  discrete  eruption  contrasting  strikingly  with  the 
gravity  of  the  general  phenomena. 

Whatever  may  be  the  clinical  form  of  the  infection,  the  results 
shown  by  the  necropsy  are  fairly  uniform.  As  in  the  adult,  there 
are  frequently  found  degenerations  of  the  liver  and  kidneys  and  small 
hemorrhages  on  the  surface  of  the  viscera,  notably  of  the  kidneys. 
In  one  case  the  suprarenal  capsules  were  the  seat  of  a  diffuse  hemor- 
rhage. Histological  examination  reveals  profounder  lesions;  myo- 
carditis is  very  frequent  and  assumes  the  same  characters  as  in  the 
adult.    The  liver  is  profoundly  altered,  and  the  changes  in  its  cells 

Fig.  42. 


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Congenital  variola. 


may  perhaps  account  in  part  for  the  frequency  and  persistence  of 
hypothermia.  Although  grave,  the  disease  is  not  necessarily  fatal. 
A  child  which  once  had  a  temperature  as  low  as  91.4°  F.  (33°  C.) 
recovered.  This  favorable  evolution  is  probably  due  to  the  fact  that 
the  mother  had  been  revaccinated  in  the  seventh  month  of  her  preg- 
nancy. Two  pustules  developed.  This  vaccination  was,  however, 
insufficient  to  establish  complete  immunity,  since  this  woman  was. 
attacked  two  months  later  by  a  discrete  variola  from  which  she  easily 
recovered.  Confinement  took  place  at  full  term,  two  days  after  the 
onset  of  the  disease  and  twenty-four  hours  before  the  development 
of  the  eruption.    The  child,  well  constituted,  weighed  six  and  one- 


CONGENITAL  INFECTIONS  AND  HEREDITY. 


591 


half  pounds,  [t  was  vaccinated  withoul  ucce  the  day  following 
its  birth.  In  spile  of  its  fine  appearance  and  the  fad  thai  it  took 
nourishment  satisfactorily,  this  child  was  hypothermic;  it  rectal 
temperature  oscillated  around  95°  P.  (35°  C.)  and  even  fell  to  93  2  I 
(34°  (!.).  Eleven  days  after  birth  the  temperature  suddenly  fell  to 
91.4°  F.  (33°  C).  In  the  eveningit  rose  to  99.2°  I  .  (37.3  '  .  and 
a  slight  erythema  appeared  on  the  skin  with  three  papule  ,  two  on 
the  arm  and  one  on  the  neck.  Three  days  later  the  papules  were 
dry  and  the  child  seemed  convalescent,  bul  on  the  sixteenth  day 
the  temperature  again  fell  to  95°  I'.  (35°  C),  to  again  rise.  Tin.-, 
thermal  variation  coincided  with  Hie  appearance  of  a  3econd  eruption 
consisting  of  three  papules  situated  on  the  scalp,  the  thigh,  and  the 

I  i.;.   4.3. 


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leg  of  the  same  side.  Two  days  later  two  new  papules  were  found 
on  the  arm  and  three  upon  the  abdomen.  The  total  number  of 
eruptive  elements  was  eleven.  The  general  condition  was  serious, 
but  the  child  took  nourishment  fairly  well.  The  following  days  the 
papules  dried,  and  an  improvement  seemed  to  follow,  but  on  the 
twenty-fourth  day  a  new  hypothermia  was  observed  accompanied 
with  vomiting  and  diarrhea.  Under  the  influence  of  subcutaneous 
injections  of  artificial  serum  the  temperature  rose  and  reached  normal 
in  a  definitive  manner  on  the  thirty-first  day.  At  the  same  time  the 
other  disturbances  disappeared  and  the  child  became  convalescent. 
This  brief  description  showed  that  the  variola  of  the  newborn  differs 
totally  from  that  of  adults.    It  is  announced  by  hypothermia,  which 


59  2  I  MIX  'TIO  US  DISEASES. 

is  in  some  cases  slight,  in  others  very  pronounced.  Jaundice  appears 
(in  only  one  of  the  eleven  children  it  was  absent).  Then  two  evolu- 
tions are  possible:  either  the  child  will  become  weak  and  die  in 
hypothermia,  without  presenting  other  symptoms,  or  else  an  eruption 
develops,  generally  coinciding  with  a  rise  in  temperature.  It  some- 
times consists  in  a  simple  rash,  but  more  often  presents  small  papules. 
The  eruption  recurs  several  times,  but  it  is  almost  always  very 
discrete.  Among  those  who  succumbed,  three  only  had  an  abundant 
eruption.  The  eruption  may  evolve  as  in  the  adult,  but  this  is 
exceptional;  the  papules  do  not  suppurate,  but  soon  dry  and  are 
covered  with  small  crusts.  Recovery  is  exceptional,  and  death  super- 
venes from  the  fourteenth  to  the  twenty-first  day  by  gradual  weak- 
ening or  syncope.  The  profound  lesions  of  the  myocardium  explain 
the  sudden  termination. 

This  peculiar  evolution  of  congenital  variola  is  of  considerable 
theoretical  interest.  In  fact,  it  recalls  the  description  of  variola  in 
the  rabbit,  such  as  we  have  described  it  with  Dr.  Weil.  We  know 
by  many  examples  that  the  pathology  of  the  first  period  of  life  is 
often  analogous  to  the  pathology  of  animals.  Thus,  tuberculosis 
takes  a  course  in  young  children  similar  to  that  in  the  small  rodents 
utilized  in  laboratories.  The  same  is  perfectly  true  of  variola :  rabbits 
inoculated  with  variolar  pus  generally  succumb  without  producing 
any  eruption;  when  they  present  any  it  consists,  as  in  newborn 
children,  of  a  limited  number  of  disseminated  papules  which  become 
covered  with  crusts  without  suppuration.  Like  children,  the  animals 
become  emaciated  and  weakened  and  succumb  in  hypothermia.  It 
is  not  only  because  the  reactionary  modes  are  analogous  in  the  new- 
born and  in  animals  that  the  evolution  is  comparable,  but  also 
because  in  both  cases  infection  is  thorough  and  overwhelming.  In 
animals  we  inject  relatively  large  quantities  of  the  virus ;  in  the  fetus 
the  microbes  also  penetrate  in  large  numbers,  as  has  been  proved 
by  the  examination  of  the  amniotic  fluid.  The  study  of  the  blood 
leads  to  similar  conclusions.  From  the  child  who  died  three  hours  after 
birth  we  took  a  drop  of  blood  immediately  after  death.  This  blood, 
examined  with  the  assistance  of  Dr.  Weil,  had  the  following  formula : 

Polynuclears 17.0  per  cent. 

Mononuclears 63.5  "  " 

Large  mononuclears 7.5  "  " 

Xfutrophile  mononuclears 10.0  "  " 

Eosinophile  mononuclears 1.0  "  " 

Eosinophiles 0.5  "  " 

Irritation  cells 0.5  "  " 


CONGENITAL  INFECTIONS  AND  HEREDITY. 

There  were;  also  found  a  great  number  of  nucleated  red  corpu  i 
Without  dwelling  upon  theoretical  consideration  which  the  study 
of  variola  in  t.l  1  r ;  newborn  gives  rise  to,  the  author  believe  thai  the 
knowledge  of  its  peculiar  evolution  is  of  certain  practical  inti 
The  (■li.'ir.'i.ciiTK  of  Hie  fever  fhart  and  of  the  eruption  imparl  to  il 
a  particular  physiognomy  and  assure  it  a  eparate  po  ition  in  the 
clinical  forms  of  this  infection. 

Intraplacental  Transmission  of  Chronic  Infections. 

It  now  remains  to  study  the  chronic  infections,  syphilis,  tubercu- 
losis, and  leprosy.  The  heredity  of  syphilis  has  been  more  thoroughly 
investigated  than  that  of  any  other  disease,  owing  to  the  fact  that 
in  this  malady  the  mode  of  contagion  is  in  general  easily  determined, 
while  in  the  case  of  tuberculosis  interpretations  are  often  diffieult. 
In  the  case  of  a  tubercular  child  the  question  may  always  be  raised 
whether  it  inherited  the  disease  or  whether  it  was  infected  after  birth 
while  living  with  its  parents.  Of  course,  syphilis  may  also  be  con- 
tracted under  the  same  conditions,  but  then  the  existence  of  a  pri- 
mary lesion  indicates  the  origin  of  the  infection  and  suffices  to  remove 
all  doubt.  Hereditary  transmission  of  syphilis  is  particularly  fre- 
quent when  both  parents  are  affected  and  the  disease  is  recent. 
After  two  or  three  years  infection  of  the  fetus  occurs  more  rarely, 
although  it  is  a  possible  event  for  a  long  period  of  time.  When  only 
one  of  the  parents  is  contaminated  the  fetus  may  still  be  infected; 
but  maternal  heredity  is  far  more  important  than  paternal.  The 
father  less  surely  transmits  syphilis;  the  inoculations  practised  by 
Mireur  have  established  in  fact  that  the  semen  is  not  virulent.  When 
the  father  alone  is  contaminated  the  fetus  dies  toward  the  sixth  or 
seventh  month  and  pregnancy  is  terminated  by  miscarriage.  If,  how- 
ever, the  child  is  born  at  full  term  it  is  often  found  to  be  free  from 
or  only  slightly  infected  by  the  disease  in  the  case  of  maternal 
syphilis.  Moreover,  some  recent  observations  tend  to  demonstrate 
that  syphilis  may  be  transmitted  during  two  generations ;  this  is  what 
results  from  the  facts  published  by  Lannelongue,  Founder,  and 
Besnier. 

In  most  cases  the  mother  is  infected  before  or  during  the  fecun- 
dation; occasionally,  however,  she  contracts  the  disease  during  preg- 
nancy. What  happens  to  the  fetus?  This  question  has  been  va- 
riously answered.  Mandrou  and  Kossowitz  have  denied  the  heredi- 
tary transmission  of  syphilis  after  conception,  while  Cullerier  is  of 

38 


594  INFJ2C TIO  US  DISEA SES. 

the  opposite  opinion.  It  seems  that  it  may  really  occur,  but  only 
when  the  infection  has  been  acquired  before  the  sixth  (Ricord)  or 
the  seventh  month  (Albernethy,  Pidoux).  After  this  epoch  the  fetus 
remains  exempt,  and  this  may  readily  be  accounted  for  by  the  fact 
that  at  the  beginning  of  infection  syphilis  remains  localized  at  the 
point  of  inoculation,  and  does  not  pass  the  limits  of  the  lymphatic 
system. 

The  manifestations  of  hereditary  syphilis  have  been  divided  by 
Fournier  into  two  groups  according  as  there  is  transmission  of  the 
virus  or  parasyphilitic  symptoms  appear.  In  the  former  instance  the 
manifestations  are  similar  to  those  in  the  adult;  the  difference  con- 
sists only  in  the  absence  of  the  initial  lesion,  which  fact  is  due  to 
the  direct  infection  of  the  blood.  This  mode  of  penetration  of  the 
pathogenic  agent  likewise  explains  the  great  rapidity  of  the  evolution 
and  the  consequent  confusion  of  the  phenomena  which  it  is  still 
customary  to  divide  into  secondary  and  tertiary.  We  hardly  need 
recall  that  syphilitic  accidents  may  appear  at  very  different  periods 
of  life;  sometimes  clinically  appreciable  manifestations  exist  at  the 
time  of  birth;  more  frequently  they  appear  toward  the  sixth  week; 
at  times  they  appear  tardily  at  the  age  of  thirteen  or  even  fifteen 
or  twenty  years  of  age.  Parasyphilitic  manifestations  shall  be 
studied  later  in  connection  with  nutritional  disturbances  which  may 
occur  in  other  infections. 

The  history  of  syphilis  likewise  furnishes  the  solution  of  several 
problems  which,  from  the  standpoint  of  general  pathology,  are  of 
great  interest.  Although  it  is  the  mother  who  commonly  transmits 
the  disease  to  her  product,  there  are  incontestable  cases  in  which  it 
has  been  inherited  from  the  father,  the  mother  remaining  absolutely 
sound.  Even  in  such  a  case,  however,  the  maternal  organism  is 
modified.  The  woman  who  gives  birth  to  a  syphilitic  child  may 
suckle  it  with  impunity,  since  she  is  in  no  danger  of  contagion.  How 
is  this  fact  to  be  interpreted?  Is  the  maternal  organism  impregnated 
by  products  secreted  by  the  microbe  of  syphilis?  Or  is  it  a  case  of 
slight  syphilis  remaining  latent,  perhaps  localized  in  the  uterus,  as 
has  been  argued  by  Frankel? 

What  has  been  demonstrated  as  true  of  syphilis  is  less  evident  with 
regard  to  tuberculosis.  There  is  one  fact  which  seems  to  be  well 
demonstrated,  viz.,  that  individuals  of  tubercular  parentage  are 
often  attacked  by  tuberculosis  at  a  more  or  less  advanced  stage. 
This  idea  is  very  old,  for  Hippocrates  admitted  the  heredity  of 


CONGENITAL   INFECTIONS  AND  HEREDITY.  595 

phthisis.     Recent  statistics  give  a  more  preci  e  idea  of  the  trans- 
mission of  the  disease  in  families.    The  stati  tic   of  Brehmer  in  the 

sanitarium  of  (Jorbersdorf  and  those  of  Detweiler  in  Falkei 
present  identical  results,  36  per  cent,  in  the  former'*  Btati  tics,  which 
were  based  upon  1.3,000  patients;  35  per  cent,  in  the  latter's,  which 
involved  a  study  of  0000  cases.  Hereditary  tuberculosis  may  become 
manifest  at  .any  age;  but,  contrary  to  whal  wa  once  believed,  it 
is  not  rare  during  early  childhood.  We  owe  to  Dr.  Landouzy  our 
knowledge  of  the  fact  that  the  victims  of  tuberculosis  during  the 
first  two  years  of  life  are  very  numerous.  While  the  fad  is  incon- 
testable, its  interpretation  is  difficult.  We  find  ourselves  in  the 
presence  of  two  diametrically  opposite  theories.  A  has  already  I  een 
stated,  some  believe  that  the  bacillus  is  transmitted,  othere  thai  it  is 
the  soil.  On  the  one  hand  it  is  asked  how  i l  is  possible  for  the  father 
to  transmit  tuberculosis  to  the  fetus  without  contaminating  the 
mother,  and  how  may  inherited  tuberculosis  remain  latenl  for  years 
and  become  manifest  at  an  advanced  age.  On  the  other  hand,  the 
example  of  syphilis  is  cited  to  explain  these  facts:  the  occurrences  are 
similar  in  both  cases,  and  why  should  we  not  admit  for  tubercuh  sis 
what  is  true  with  regard  to  syphilis?  Such  is  the  reasoning.  U  I 
us  now  consider  the  results  of  clinical  observation  and  experimen- 
tation. 

There  are  some  observations  on  record  in  which  children  suc- 
cumbed so  rapidly  that  it  is  hardly  possible  to  presume  a  contagion 
after  birth.  But  these  facts  may  leave  some  doubt  in  the  mind,  since 
it  must  be  admitted  that,  in  a  child  predisposed  by  heredity,  acquired 
tuberculosis  may  run  a  rapid  course  and  prove  fatal  in  a  few  weeks. 
This  would  be  an  evolution  similar  to  that  which  is  observed  in 
animals  inoculated  in  laboratories.  The  same  thing  may  not  be  said 
of  those  cases  in  which  tubercular  lesions  were  found  in  stillborn 
fetuses.  Some  such  facts  have  been  observed  in  the  human  species. 
The  first  observations  are  due  to  Ollendorf,  Peter,  S.  Charrin,  and 
Berti,  and  belonged  to  an  epoch  when  Koch's  bacillus  was  yet 
unknown.  More  important  is  the  observation  of  Sabouraud :  a  child 
born  of  a  mother  suffering  from  acute  miliary  tuberculosis  succumbed 
eleven  days  after  birth.  At  the  necropsj'  the  liver  and  spleen  were 
found  full  of  tubercular  granulations  in  which  the  presence  of  the 
characteristic  bacillus  was  detected.  In  an  observation  reported  by 
Armanni  the  liver  and  spleen  of  a  fetus  issued  of  a  tubercular  mother 
were  inoculated  into  guinea-pigs  and  gave  tuberculosis  to  these  ani- 


596  INFECTIOUS  DISEASES. 

mals.    In  a  case  reported  by  Bar  and  Renon  the  blood  of  the  umbili- 
cal cord  contained  Koch's  bacillus. 

Intraplacental  transmissibility  is,  therefore,  incontestable ;  it  is, 
however,  much  less  frequent  in  the  human  species  than  in  animals, 
especially  in  the  bovine  species.  Dr.  Chauveau  has  found  tubercles 
several  times  in  fetuses  of  consumptive  cows.  By  inquiring  of  1165 
Danish  veterinarians,  Bang  found  that  32  of  them  had  observed 
tubercles  in  newborn  calves.  While  most  of  these  cases  may  be 
regarded  as  doubtful,  since  no  mention  is  made  of  the  presence  of 
Koch's  bacillus,  such  criticism  cannot  be  addressed  to  the  observa- 
tions of  Johne,  De  Malvoz,  and  Brouwier.  In  fetuses  from  tubercular 
cows  these  authors  not  only  found  tubercles  but  bacilli  as  well. 
Misselwitz  and  Bang  have  reported  similar  facts. 

To  complete  the  data  of  observation  it  was  necessary  to  resort  to 
experimentation.  The  results  obtained  seem  to  be  somewhat  con- 
tradictory. To  the  positive  findings  of  Landouzy  and  Martin  are 
opposed  negative  results  of  other  experimenters.  On  the  other 
hand,  De  Renzi,  who  experimented  upon  eighteen  pregnant  guinea- 
pigs,  found  tubercles  in  the  fetus  five  times.  In  order  that  there  may 
be  contamination,  the  inoculation  must  be  practised  at  least  thirty- 
four  days  before  the  birth  of  the  }roung.  In  several  cases  these 
perished  in  marasmus  without  becoming  tuberculous.  Whatever  the 
final  solution  may  be,  the  results  obtained  in  guinea-pigs  should  not 
be  applied  to  man,  as  there  is  no  proof  that  the  same  is  true  of  man. 
For,  by  inoculating  the  white  mouse,  Gartner  found  that  the  tubercle 
bacillus  passed  to  the  fetus,  and  the  same  experimenter  saw  the 
bacilli  infecting  the  eggs  of  tubercular  canary  birds,  while  the  result 
was  negative  in  hens. 

A  last  question  is  whether  a  tubercular  father  may  beget  a  tuber- 
cular child;  in  other  words  whether  the  semen  may  be  the  vehicle 
for  the  bacilli.  As  to  this  point  there  seems  to  be  no  doubt.  Even 
when  the  genital  organs  seem  to  be  sound  the  semen  of  a  tubercular 
subject  may  contain  the  bacilli,  as  has  been  demonstrated  by  the 
researches  of  Landouzy  and  Martin,  Weigert,  Jani,  Bozzolo,  and 
Niepce.  Can,  however,  the  bacillus  infect  the  ovum?  Baumgarten, 
who  is  one  of  the  most  ardent  advocates  of  the  heredity  of  tubercu- 
losis, does  not  hesitate  to  answer  in  the  affirmative.  In  one  case, 
having  artificially  fecundated  a  rabbit  with  the  semen  of  a  tubercu- 
lar rabbit,  he  detected  the  bacillus  in  the  ovum.  This  curious 
observation  does  not  lead  to  a  firm  conclusion,  since  it  is  not  known 


CONGENITAL  INFECTIONS  AND  HEREDITY.  :,\u 

what  would  become  of  this  bacillus  or  of  the  ovum  the  bacillus 
might  not  proliferate  or  the  ovum  mighl  be  killed  by  the  microbe, 

and  thus  uoi,  In;  developed.  If  is  true  that  Baumgarten  belli  ve  thai 
the  tissues  of  the  fetus  and  of  the  newborn  oppose  a  considerable 
resistance  to  the  infectious  agent,  and,  to  explain  tardy  hereditary 

tuberculosis,  lie  contends  that  (lie  bacilli  may  long  sojourn  in  the 
lymphatic  glands  and  (he  lnuie  luarrowwithoul  causing  any  disturb- 
ance. Later,  under  the  influence  of  some  occasional  cause— an 
inflammation  or  a  traumatism  the  tissues  lose  in  some  degree  their 
vitality  and  are  attacked  by  the  microbes.  This  conception  is  sup- 
ported by  the  researches  of  Landouzy  and  Martin  and  by  the  more 
recent  investigations  of  Birch-Hirschfeld  and  Schmorl.  These 
authors  demonstrated  that  in  fetuses  of  tubercular  mothers  the 
apparently  sound  organs  sometimes  contain  the  specific  bacillus. 
Maffucci's  experiments  may  also  be  adduced  in  supporl  of  tardy 
inherited  tuberculosis.  This  author,  by  inoculating  various  microbes 
into  the  eggs  of  hens,  noticed  that  infection  did  not  become  manifest 
until  some  time  after  the  eggs  were  hatched. 

When  a  fetus  of  a  mammalian  is  born  with  tubercular  lesions  the 
latter  present  some  interesting  peculiarities.  Congenital  differs  from 
acquired  tuberculosis,  not  in  the  anatomical  characters  of  the  tuber- 
cles, but  in  their  localization.  The  liver  is  the  organ  most  frequently 
and  seriously  involved,  owing  to  the  fact  that  the  bacilli  conveyed 
through  the  umbilical  vein  first  colonize  in  the  liver. 

In  brief  such  are  the  principal  facts  which  may  be  advanced  fro 
and  con  in  the  doctrine  of  hereditary  tuberculosis.  In  spite  of  the 
great  number  of  works  published  on  this  subject,  the  answer  to  the 
questions  which  we  had  to  solve  has  not  yet  been  given.  It  seems 
to  be  perfectly  well  demonstrated  hy  the  observations  of  Landouzy. 
Queyrat,  Hayen,  Damaschino,  and  Lannelongue  that  tuberculosis  is 
far  from  rare  in  young  children,  and  that  children  born  of  infected 
parents  are  attacked  by  the  disease  with  alarming  frequency.  The 
transmission  of  the  bacilli  is  also  established  by  a  few  observations; 
but  facts  of  this  kind,  when  submitted  to  severe  criticism,  as  was 
done  by  Dr.  Kiiss,  appear  to  be  altogether  exceptional.  In  the 
majority  of  cases  parents  suffering  from  tuberculosis  transmit  to 
their  children  nothing  more  than  a  predisposition  to  contract  the 
disease.  The  children  are  born  with  paratubercular  alterations,  and 
some  of  their  organs  do  not  attain  full  development.  But  they  are 
not  tubercu'ous.    Schreiber,  Hutinel,  and  Landouzy  injected  tuber- 


598  I  N  FECTIO  US  DISEASES. 

culin  into  children  born  of  tubercular  parents  without  ever  obtaining 
the  characteristic  reaction.  Inheritance  of  the  germ  itself  is,  there- 
fore, the  exception. 

The  same  conclusions  seem  to  be  reached  as  regards  leprosy.1 
Danielssen,  Bock,  and  Zambaco  attach  some  importance  to  the 
hereditary  transmission  of  this  disease.  On  the  other  hand,  Zambaco 
admits  a  tardy  heredity  and  holds  congenital  leprosy  to  be  alto- 
gether exceptional.  It  is  well  to  note,  however,  that  there  is  not  a 
single  case  in  which  bacteriological  examination  was  made.  In  most 
instances  marriage  of  leprous  individuals  leads  to  sterility,  abortion, 
and  non-viability.  The  children  are  weak  and  cachectic  and  die 
under  age. 

Dystrophies  of  Infectious  Origin.  Infection  of  the  parents,  and 
particularly  chronic  infection  of  the  mother,  may  impose  upon  the 
fetus  a  defective  nutrition.  The  result  is  a  series  of  new  disorders 
which  may  be  included  under  the  name  of  parainfections.  In  some 
cases  one  of  the  two  parents  is  convalescent  from  a  more  or  less  grave 
infection  at  the  moment  of  conception;  the  product  is  then  a  weak- 
ling, developed  imperfectly  and  predisposed  to  contract  various 
infections,  notably  tuberculosis.  In  syphilis  especially  numerous 
examples  of  parainfectious  disorders  are  observed.  Prof.  Fournier 
has  made  a  perfect  study  of  these  which  we  shall  sum  up  in  a  few 
words. 

In  the  first  place,  there  is  a  fetal  cachexia  which  causes  death  at 
a  more  or  less  advanced  period  of  gestation.  If  the  fetus  does  not 
die  it  may  be  born  prematurely;  at  all  events  it  comes  into  the  world 
as  a  weakling  which  develops  very  slowly.  The  dystrophy  is  ex- 
pressed after  birth  by  incomplete  growth;  evolution  is  retarded; 
the  teeth  do  not  appear  at  the  regular  periods;  the  evidences  of 
puberty  are  delayed;  menstruation  is  not  established;  the  beard  is 
absent.  The  individual  remains  imperfectly  developed;  the  genital 
organs,  testicles,  and  penis  are  rudimentary;  the  bones  are  not  suffi- 
ciently rich  in  calcium  salts;  the  brain  is  often  atrophied;  the  intel- 
ligence is  more  or  less  dull.  A  third  group  of  facts  is  represented  by 
congenital  deformities :  syphilis  is  often  found  in  the  parents  of  indi- 
viduals suffering  from  club-foot,  spina  bifida,  harelip,  and  micro- 
cephalic and  hydrocephalic  conditions.  Finally,  the  children  of 
syphilitic  parents  are  predisposed  to  certain  affections  of  nutritional 

1  Dom  Santon.     La  L6pro.se,  Paris,  1901. 


CONGENITAL  INFECTIONS  AND  HEREDITY.  599 

order  or  of  infectious  origin.  Although  Parrol  erred  in  considering 
rickets  a  manifestation  of  syphilis,  there  is  no  doubt  thai  thi  affec- 
tion is  very  frequent  among  children  of  syphilitics.  [n  thi  c 
however,  the  manifestation  is  of  the  paraspecific  kind:  yphilic  hae 
simply  played  the  r61e  of  a  predisposing  cause,  tte  influence  in  the 
appearance  of  nervous  affections,  such  as  Little'i  disease,  or  in  the 
more  or  less  early  development  of  tuberculosis  and  in  the  occurrence 
of  meningitis  should  be  interpreted  in  this  manner. 

What  we  have  stated  in  regard  to  syphilis  may  be  repeated  with 
reference  to  tuberculosis.  We  find  the  same  difficult,  incomplete, 
and  slow  development  in  children.  Their  stature  may  sometimes  be 
high,  but  their  bones  an1  fragile,  their  articulations  are  clumsy,  their 
muscles  thin.  The  skin  is  thin  and  transparent;  the  hair  long  and 
silky;  the  genital  organs  imperfectly  developed;  the  fingers  are  Blen- 
der, and  the  nails  hyportrophied.  The  thorax  is  flat  and  narrow;  the 
lungs  small  and  often  emphysematous;  the  liver  is  lobulated.  Breh- 
mer  and  Beneke  have  noted  the  weakness  of  the  arterial  system, 
stricture  of  the  aorta  and  of  the  pulmonary  artery.  These  children 
are  predisposed  to  chlorosis  and  hysteria.  Some  of  them  succumb 
very  young,  being  carried  off  by  convulsions.  It  is  not  rare  to 
observe  several  children  die  under  age,  before  tuberculosis  has  clearly 
manifested  itself  in  the  parents. 

Congenital  Predisposition  and  Immunity. 

Heredity  accounts  for  a  great  number  of  facts  concerning  predis- 
position and  immunity.  Some  families  contract  certain  infectious 
diseases  with  the  greatest  facility  and  during  several  generations. 
Certain  families  are  particularly  subject  to  tuberculosis,  diphtheria, 
scarlatina,  or  erysipelas.  On  the  other  hand,  there  are  immunities 
of  families,  communities,  and  races.  It  is  certain,  for  example,  that 
the  infections  imported  into  countries  where  they  were  unknown 
prove  extremely  fatal.  Such  is  the  case  with  syphilis  and  the  erup- 
tive fevers.  On  the  European  Continent  these  diseases  are  relatively 
benign,  owing  to  ancestral  impregnation.  There  is  created  in  indi- 
viduals a  certain  degree  of  immunity,  or  at  least  resistance,  which  is 
transmitted  to  successive  generations. 

This  leads  us  to  stud)T  the  immunity  which  ma)*  be  acquired  by 
the  fetus  in  utero.  As  has  been  remarked  by  Vaillard,  two  events 
are  possible :  the  mother  may  contract  the  disease  during  gestation, 
or  one  of  the  two  parents  may  be  diseased  before  fecundation.     In 


600  I MECTIOUS  DISEASES. 

the  former  case  the  fetus  participates  in  the  disease  either  because 
the  microbes  pass  through  the  placenta  and  invade  it  or  because  the 
placenta  forms  a  perfect  filter  against  the  figurate  elements  and 
allows  only  the  soluble  products  to  pass.  Then  disease  of  the  fetus, 
complete  or  incomplete,  occurs,  and  the  immunity  is  similar  to  that 
established  in  the  adult.  In  the  latter  case,  on  the  contrary,  the 
disease  having  been  cured  at  the  moment  of  conception,  there  is 
merely  transmission  of  an  acquired  character.  The  immunity  con- 
ferred upon  the  fetus  by  a  disease  of  the  mother  is  a  result  estab- 
lished b}r  numerous  observations.  As  has  already  been  stated,  a 
child  born  of  a  mother  afflicted  by  variola,  and  coming  into  the  world 
without  any  appreciable  manifestation  of  the  disease,  may  neverthe- 
less have  acquired  immunity  against  this  infection.  Vaccinia  be- 
haves in  the  same  manner,  at  least  in  certain  cases,  since  the  results 
are  quite  variable.  Burckhard  experimented  upon  eight  children; 
four  of  them  were  born  of  women  who  had  been  successfully  vac- 
cinated during  gestation.  The  children  proved  iimnune,  one  of  them 
continuing  to  be  so  at  the  end  of  six  months.  In  two  cases  re  vac- 
cination gave  a  doubtful  result,  and  one  of  the  two  children  born  of 
these  women  proved  refractory.  The  author  likewise  observed  that 
one  of  the  two  children  born  of  mothers  who  had  been  re  vaccinated 
without  success  at  the  end  of  their  pregnancy  proved  refractory. 
The  results  obtained  by  Chambrelent  were  almost  identical.  This 
author  vaccinated  forty  women;  he  obtained  a  true  vaccinia  in  the 
children  only  seven  times.  We  find  quite  different  figures  in  Behm/s 
researches.  Out  of  twenty-nine  children  observed  by  this  author, 
only  two  proved  refractory.  Finally,  Wolff,  having  successfully 
vaccinated  seventeen  women,  vaccinated  with  equal  success  all  the 
children  from  one  to  six  days  after  birth.  On  the  other  hand,  Lopp 
observed  vaccinal  immunity  in  children,  but  this  immunity  did  not 
last  more  than  from  six  to  eighteen  months.  These  contradictory 
results  point  to  the  conclusion  that  vaccinal  immunity,  like  infection 
itself,  is  transmitted  only  in  about  half  the  cases. 

One  of  the  human  diseases  which  has  served  most  for  the  study 
of  these  important  questions  of  general  pathology  is  syphilis.  We 
have  already  pointed  out  that  a  woman  bearing  a  syphilitic  fetus, 
even  when  she  does  not  contract  the  disease,  becomes  immune 
against  the  infection;  she  may  with  impunity  suckle  her  child  which 
would  contaminate  a  strange  nurse.  This  is  what  is  called  Colles' 
law.     This  law  is  confirmed  by  an  experiment  of  Caspary :  A  woman 


CONGENITAL  INFECTIONS  AND  HEREDITY  601 

fecundated  \>y  a  syphilitic,  man,  who  was  apparently  cured,  aborted 
at  the  .sixth  month.    The  mother,  who  bad  presented  do  specific 

manifestations  ;i,i,  ;i,iiy  lime,  consented  lo  be  inoculated,  and  pri 
to  be  immune.  In  oilier  cases  the  resull  is  differenl :  the  fetui  does 
not  communicate  immunity  lo  the  mother,  hul  the  di  ea  e  itself. 
This  is  called  syphilis  by  conception.  Diday  was  one  of  the  fii 
draw  attention  to  these  facts,  the  Dumber  of  which  at  pre  en1  is 
quite  considerable.  Syphilis  by  conception  runs  itt  '''Hire  like  con- 
genital syphilis.  In  both  instances  infection  is  effected  through  the 
blood.  The  pathogenic  agent  penetrates  directly  the  circulatory 
system.  Hence,  the  absence  of  all  primary  manifestations.  A  pr<  g- 
nant  woman  will  then  present  symptoms  of  secondary  syphilis  with- 
out ever  having  either  chancre  or  enlargeinenl  of  the  lymphatic 
glands. 

Profeta  has  formulated  a  law  similar  to  that  of  Colics.  If  a  child 
born  of  a  syphilitic  mother  is  found  in  sound  condition  it  has  acqu  i  red 
immunity  against  syphilis  and  does  not  contract  it  through  the  milk 
or  caresses  of  the  mother.  This  is  a  result  analogous  to  that  observed 
in  other  infections,  for  example,  variola. 

Among  the  experimental  diseases  anthrax  is  the  one  that  has  been 
the  subject  of  the  most  interesting  investigations  bearing  upon  these 
questions.  Chauveau,  after  having  inoculated  Algerian  sheep  at  the 
end  of  gestation,  observed  that  the  young  born  of  them  presenter] 
no  morbid  symptoms  when  they  were  inoculated  with  the  bacillus. 
This  is  a  new  illustration  of  the  immunity  which  may  be  acquired 
by  the  fetus.  Anthrax  has  also  been  employed  to  demonstrate  ex- 
perimentally the  truth  of  Colics'  law.  Lingaard  inoculated  this 
disease  into  fetuses  of  rabbits  while  yet  in  the  uterus.  The  young 
died,  while  in  most  cases  the  mothers  survived.  Microscopic  exam- 
ination and  cultivation  revealed  no  bacilli  in  the  maternal  organisms, 
and  yet  the  animals  had  acquired  perfect  immunity,  which  still 
persisted  at  the  end  of  eight  months.  The  fact  is  the  more  interest- 
ing, as  all  experimenters  are  aware  how  difficult  it  is  to  vaccinate 
the  rabbit  against  anthrax.  Moreover,  Lingaard  established  that,  in 
order  to  confer  immunity,  the  fetus  must  be  inoculated  at  least 
thirty-six  hours  before  its  expulsion;  the  other  fetuses  may  become 
refractory  if  the  inoculated  young  remain  six  days  in  the  uterus. 
In  some  instances,  as  in  syphilis  by  conception,  the  mother  contracts 
anthrax  infection;  but  then  placental  alterations,  through  which  the 
passage  of  the  bacilli  may  be  traced,  exist.    When  the  mother  resists 


602  INFEt  'TIO  US  DISEASES. 

the  pathogonic  agents  have  their  scat  exclusively  in  the  fetal  blood- 
vessels of  the  placenta. 

On  the  basis  of  these  experimental  facts  Chauveau  established  his 
famous  theory  of  immunity.  After  the  experiments  of  Brauell  and 
of  Davaine,  the  placenta  was  supposed  to  constitute  a  perfect  filter; 
immunity  was  attributed  to  the  transmission  of  soluble  substances 
produced  within  the  maternal  organism  under  the  influence  of 
anthrax.  It  is  at  present  known  that  the  placenta  is  in  some  cases 
traversed  by  anthrax  bacilli,  and,  therefore,  Chauveau's  deductions 
have  been  questioned.  It  has  been  asked  whether  congenital  immun- 
ity is  not  due  to  the  passage  of  the  bacilli  which  are  too  small  in 
number  to  kill  the  fetus,  but  sufficient  to  vaccinate  it.  To  this 
objection  Chauveau  answered  that  the  passage  of  the  bacilli  through 
the  placenta  is  an  inconstant  phenomenon,  while  in  all  his  experi- 
ments, fortjr  in  number,  the  young  had  acquired  immunity. 

The  most  important  experiments  from  the  standpoint  of  hereditary 
transmission  of  immunity  are  those  in  which  animals  were  vaccinated 
by  living  microbes  or  by  soluble  products  more  or  less  long  before 
fecundation.  The  experiments  pursued  with  symptomatic  anthrax 
had  already  demonstrated  that  animals  born  of  mothers  vaccinated 
even  some  time  before  fecundation  often  prove  refractory  (Arloing, 
Cornevin,  Thomas). 

Studying  the  transmission  of  immunity  in  animals  vaccinated 
against  vegetable  poisons,  such  as  abrin  and  ricin,  or  against  tetanus, 
Ehrlich  arrived  at  the  following  conclusions:  The  father  does  not 
communicate  immunity  to  his  offspring;  the  mother  may  impart  a 
transitory  immunity  which  lasts  three  or  four  weeks  and  is  not  trans- 
mitted from  generation  to  generation.  This  is  a  passive  immunity 
due  to  intraplacental  passage  of  antitoxin  contained  in  the  maternal 
organism.  By  studying  diphtheria,  Wernicke  reached  identical 
results.  On  the  other  hand,  Tizzoni  and  Centanni,  experimenting  with 
tetanus  and  hydrophobia;  Charrin  and  Gley  with  the  bacillus  pyo- 
cyaneus  reached  the  conclusion  that  the  male  is  equally  apt  to 
transmit  immunity.  There  was,  therefore,  hereditary  transmission 
of  a  character  acquired  by  the  somatic  cells.  The  question  was 
taken  up  by  Vaillard  in  a  work  which  may  be  held  as  a  model  of 
fine  experimental  criticism.  Animals  were  vaccinated  against  tet- 
anus and  cholera  by  means  of  soluble  products  and  against  anthrax 
by  means  of  living  microbes.  When  a  strong  immunization  was 
obtained  the  animals  were  mated.    The  young  born  of  a  hypervac- 


CONGENITAL  INFECTIONS    \M>  HEREDITY. 

ciliated  father  and  a  normal  mother  never  presented  the  sligl 
degree  of  resistance.  The  vaccinated  femal<  invariably  communi- 
cated to  their  offspring  the  immunity  which  they  had  acquired.  Bui 
immunity  thus  transmitted  is  no1  permanent.  Ii  may,  however,  be 
prolonged  by  lactation)  the  mammary  secretion  furnj  h<  ome  anti- 
dote to  the  nursling.  This  second  factor  seem  to  plaj  the  more 
important  role  The  researches  of  Vaillard  tend  to  how,  however, 
that  we  must  not  rely  too  much  upon  lactation,  for  milk  i  active 
only  in  certain  animal  species,  the  mouse,  for  example. 

Three  theories  have  been  advanced  to  explain  the  intrauterine 
transmission  of  immunity.  Duclaux,  Arloing,  and  especially  Charrin 
and  Gley  have  advanced  a  cellular  theory.  According  to  these 
authors  the  cells  acquire  a  certain  activity  under  the  influence  of 
vaccination;  the  cells  of  generation,  influenced  like  the  other  cells, 
impart  their  mode  of  life  to  the  being  which  is  developed;  the  daugh- 
ter cells  continue  the  physiological  activity  of  their  mother  cells, 
and,  like  these,  they  are  capable  of  secreting  germicidal  or  anti- 
toxic substances  and  exercising  phagocytic  action.  This  theory 
well  explains  the  transmission  of  immunity  by  the  father;  but  we 
know  that  the  view  is  disputed  and  rejected  by  the  majority  of 
authors. 

The  second  theory  is  that  of  Ehrlich,  according  to  which  the 
immunity  of  the  fetus  is  due  to  the  passage  through  the  placenta 
of  antitoxic  and  germicidal  substances  from  the  mother.  This  the<  try 
would  evidently  be  annihilated  if  it  was  demonstrate*  1  some  day  that 
the  father  also  may  transmit  immunity.  According  to  Ehrlich,  the 
mother  alone  has  this  power,  and  the  immunity  of  the  fetus  is  a 
passive  one,  analogous  to  that  obtained  outside  of  the  uterus  by 
means  of  serumtherapy.  Vaillard  admits  the  passage  of  the  active 
substances  of  the  serum  through  the  placenta,  but,  following  the 
ideas  of  Metchnikoff,  lie  does  not  accept  the  theory  that  immunity 
is  effected  only  by  means  of  the  fluids  of  the  organism.  He  remarks 
that  there  is  not  alwajrs  a  relation  between  the  state  of  the  fluids 
and  the  degree  of  immunity  and  believes  that  the  active  substances 
of  the  mother,  passing  through  the  placenta,  stimulate  the  fetal 
organism,  render  the  cells  insensible  to  intoxication,  increase  the 
energy  of  the  phagocytes,  and  even  give  rise  to  the  secretion  of  anti- 
toxins. This  is  to  extend  to  the  fetus  the  general  theory  which  is 
accepted  by  some  authorities  concerning  immunity.  Without  dwell- 
ing upon  the  discussion,  we  shall  only  note  that  the  present  tendency 


604  INFECTIOUS  DISEASES. 

is  to  attribute  immunity,  as  has  already  been  maintained  by  Chau- 
veau,  to  the  intraplaoental  passage  of  soluble  substances.  Fetal 
immunity  is  comparable  to  that  produced  by  a  preventive  injection 
of  serum;  it  is,  perhaps,  a  little  more  lasting,  since  the  impregnation 
is  longer,  but,  like  all  passive  immunity,  it  rapidly  disappears. 

Conclusions.  Summing  up  the  principal  results  arrived  at,  we  see 
that  several  results  are  possible.  In  some  cases  the  microbes  produce 
in  the  fetus  a  graver  infection  than  that  of  the  mother.  By  vac- 
cinating pregnant  sheep  we  often  see  the  fetus  die  and  expelled  by 
an  abortion.  The  death  of  the  fetus  killed  by  the  infection  which 
is  resisted  by  the  mother  explains  a  certain  number  of  abortions 
observed  in  the  human  species,  for  example,  in  pneumonia,  typhoid 
fever,  and  syphilis. 

Not  infrequently,  the  fetal  disease  is  similar  to  that  of  the  adult. 
Such,  in  some  cases  at  least,  are  variola  and  syphilis.  In  other 
instances  the  fetal  affection  differs  not  by  its  anatomical  characters, 
but  by  its  peculiar  localization.  Such  is  the  case  in  congenital  tuber- 
culosis, which  invades  particularly  the  liver.  It  may  be  said  that  in 
almost  all  fetal  infections  the  liver  is  most  profoundly  affected  and 
contains  the  greatest  number  of  pathogenic  agents.  This  is  readily 
conceivable  in  view  of  the  fact  that  this  gland  is  placed  like  a  barrier 
at  the  root  of  the  bloodvessels  coming  from  the  placenta.  There  are 
diseases  in  which  the  fetus  contains  pathogenic  microbes  without  the 
existence  of  any  appreciable  lesions.  Thus,  as  has  already  been 
stated,  in  anthrax  the  blood  does  not  present  the  agglutinating  char- 
acter which  is  so  manifest  in  the  adult.  In  typhoid  fever  the  fetus 
does  not  present  the  alterations  in  Peyer's  patches  nor  splenic  hyper- 
trophy. 

It  is  also  possible  that  a  child  born  of  an  infected  mother  presents 
at  birth  no  morbid  manifestations,  but,  after  several  years,  symp- 
toms of  this  infection  may  become  manifest.  This  has  been  demon- 
strated in  syphilis,  and  is  supposed  to  be  true  of  tuberculosis.  In 
other  instances  the  infections  of  the  parents  may  impose  upon  the 
fetus  an  abnormal  mode  of  nutrition  which  may  persist  throughout 
life.  Dystrophies,  congenital  malformations,  and  predisposition  to 
the  most  varied  infections  may  result.  However,  infections  of  the 
parents  do  not  always  produce  disturbances  in  the  children.  There 
are  cases  in  which  heredity  is  not  evidenced  by  any  morbid  symp- 
toms. In  these  instances  the  child  may  be  influenced  by  the  maternal 
disease   and  acquire  immunity.     This  intrauterine  vaccination  is 


CONGENITAL  INFECTIONS  AND  HEREDITY.  606 

inconstant.     In  a  l;i„st  category  of  cases,  we  place  those  in  tan© 
which  the  child  comes  info  flu:  world  uninfluenced  by  'Ik-  parental 
disease. 

Such  arc  flic  principal  eventualitie  thai  may  \><-  observed.  We 
see  that  the  results  are  widely  variable,  from  the  grave  and  rapidly 
fatal  infection  to  the  absence  of  all  symptoms,  and  even  of  all  morbid 
impregnation. 


CHAPTER   XXL 

DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES. 

Various  Procedures  of  Diagnosis.  Clinical  Procedures.  Bacteriological  Procedures. 
Research  of  Pathogenic  Agents  by  Microscopic  Examination  and  by  Cultivation. 
Inoculations  from  a  Diagnostic  Standpoint.  Cytological  Examination  of  the  Blood, 
Fluids,  and  Exudates.  The  Vesicatory  Test.  Diagnosis  According  to  Chemical 
Modifications  in  Fluids.  Research  of  Agglutination.  Modifications  in  the  Urinary 
Secretion.  The  Diazo  Reaction.  Diagnosis  by  Therapeutics.  Diagnosis  by  Microbic 
Toxins.  Tuberculin  and  Mallein.  Diagnostic  Problems.  Questions  Concerning  the 
Seed  and  the  Soil.  Importance  of  a  Complete  Diagnosis  for  Prognosis.  The  Bases 
of  Prognosis.  Personal  Statistics:  Mortalit}'  in  8832  Cases  of  Infectious  Diseases. 
Influence  of  Age  and  Sex  upon  Mortality.  Variation  of  Gravity  According  to 
Various  Epidemics.  Importance  of  Etiological  Conditions  and  of  Mode  of  Invasion. 
Bases  of  Prognosis  during  the  Stationary  Period.  Study  of  the  Local  Lesion, 
General  Phenomena,  and  State  of  the  Principal  Organs.  Importance  of  Previous 
Diseases  and  Lesions  for  Diagnosis.  Prognosis  for  the  Present,  for  the  Future,  and 
for  the  Descendants.     Comparison  of  Clinical  and  Bacteriological  Methods. 

There  are  two  methods  for  establishing  diagnosis — one,  clinical, 
the  other  the  laboratory  method.  The  clinical  method  consists  in 
inquiry  as  to  the  sensations  experienced  by  the  patient,  the  disturb- 
ances that  may  be  seen,  and  the  physical  signs  that  may  be  detected. 
It  is  customary,  however,  to  complete  the  information  thus  obtained 
by  two  more  scientific  procedures,  namely,  the  determination  of  the 
temperature  by  means  of  the  thermometer,  and  chemical  analysis 
of  the  urine. 

The  advance  in  bacteriology  and  the  importance  recently  acquired 
by  experimental  investigations  have  led  to  other  procedures.  It 
has  been  asserted  that  clinical  investigations  are  absolutely  inade- 
quate. It  has  been  said  that  in  order  to  succeed  in  determining 
the  nature  of  a  malady  it  is  necessary  to  resort  to  methods  of 
precision,  to  search  for  bacteria  in  exudates,  secretions,  and  ex- 
cretions, and  to  study  the  chemical  and  histological  modifications 
in  the  organs,  tissues  and  fluids.  The  consequence  is  that,  in  a 
great  number  of  cases,  it  is  possible  to  make  a  diagnosis  without 
examining  the  patient.  It  suffices  to  look  for  Koch's  or  Loeffler's 
bacillus  in  order  to  diagnose  tuberculosis  or  diphtheria.  It  is  in  no 
wise  pretended  to  cast  doubt  upon  the  service  which  may  be  rendered 
clinicians  by  laboratory  researches,  but  simply  to  say  that  these 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DI8EA    E        607 

two  methods  are  not  to  be  opposed  to  each  other.  Some  authors 
have  recently  taken  certain  pleasure  in  pointing  to  the  erroi 
clinical  diagnosis.  They  seem  to  be  happy  to  demon  trate  thai  the 
old  methods  give  but  illusive  information.  For  some  physicians 
the  diagnosis  of  diphtheria  is  absolutely  impo  ible  without  cultiva- 
tion in  serum,  [t  seems  to  me  thai  this  tendency  leads  to  deplorable 
conclusions  in  practical  medicine,  [tshould  not  be  overlooked  thai 
in  many  enscs  the  physician  cannot  possibly  resorl  to  new  methods. 
A  practitioner  in  a  country  place,  for  example,  far  from  scientific 
centres,  can  hardly  have  the  facilities  for  making  cultures.  If  it  i- 
a  case  of  acute  infection,  and  if ,  guided  by  new  ideas,  he  sends  the 
suspicious  exudates  to  the  aearesl  faculty,  the  chancee  are  thai  he 
will  receive  an  answer  when  the  evolution  of  the  disease  ie  al  an 
end — i.  e.,  when  the  patient  has  recovered  or  is  dead.  This  does 
not  mean  that  scientific  datn  are  to  be  rejected.  Those  who  are 
practising  in  cities  possessing  laboratories,  and  especially  those  who 
attend  in  hospitals,  must  resort  to  modern  methods  of  investigation. 
This,  however,  should  not  be  done  with  the  idea  of  opposing  the 
results  furnished  by  cultivation  to  information  given  by  clinical 
observation — to  show  the  superiority  of  the  former  and  the  un- 
certainty of  the  latter.  He  who  can  combine  observation  and 
experimentation  must  decide  what  modifications  must  be  introduced 
into  nosological  classification  and  give  greater  precision  to  simple 
observations.  Bacteriology  must  be  resorted  to,  not  to  show  the 
insufficiency  of  clinical  observation,  but  as  a  means  of  more  closely 
approaching  the  truth.  Those  who  have  a  hospital  with  a  laboratory 
at  their  disposal  must  compare  the  results  furnished  by  differ. -n? 
procedures  of  exploration,  and,  far  from  bringing  out  their  antag- 
onisms, seek  to  harmonize  them.  It  seems  to  me  that  we  must  not 
as  yet  ask  too  much  of  bacteriological  data.  "We  shall  presently 
show  that  they  sometimes  furnish  indications  less  certain  than  those 
yielded  by  simpler  procedures  of  exploration. 

Search  for  Pathogenic  Agents  by  Microscopic  Examination  and 
Cultivation.  The  means  now  at  our  disposal  for  making  a  scientific 
diagnosis  maybe  divided  into  three  groups:  the  search  for  microbes, 
the  study  of  modifications  in  cells  and  fluids,  and  the  specific  action 
of  certain  toxins. 

The  search  for  microbes  is  made  by  microscopic  examination, 
cultivation,  and  inoculation  into  animals.  Microscopic  examination 
is  applied  to  secretions,  dejections,  and  inflammatory  foci:  more 


608  IXFECTIOUS  DISEASES. 

rarely  to  the  blood  and  the  interstitial  fluids  of  organs.  It  renders 
very  remarkable  service  in  determining  the  nature  of  an  inflam- 
matory lesion,  an  effusion  into  a  serous  cavity,  an  abscess,  and  a 
gangrenous  focus.  When  a  focus  does  not  communicate  with  the 
exterior — i.  c,  when  it  has  not  been  invaded  by  common  bacteria 
from  without,  one  may  be  nearly  certain  that  when  a  microbe  is 
found  it  is  the  agent  of  the  morbid  process.  At  any  rate  the  pro- 
cedure is  very  simple,  and  the  harmlessness  of  exploratory  puncture 
justifies  this  sort  of  investigation  in  most  cases.  On  the  contrary, 
when  the  morbid  focus  is  not  closed,  it  generally  contains  several 
microbic  species.  Hence,  interpretation  becomes  far  more  difficult. 
In  some  cases  a  clearly  differentiated  specific  bacterium  is  found 
and  is  responsible  for  the  morbid  phenomena.  Such,  for  instance, 
is  the  case  when  actinomyces  are  detected  in  a  purulent  fluid  or 
the  tubercle  bacillus  in  sputa.  The  result  has  no  importance, 
however,  except  when  it  is  positive.  The  absence  of  Koch's  bacillus 
in  a  sputum  does  not  at  all  imply  the  absence  of  tuberculosis.  Never- 
theless, the  scientific  character  of  these  researches  gives  an  exagger- 
ated importance  to  the  results  obtained.  The  fact  that  the  bacilli 
are  absent  from  the  sputum  when  the  morbid  foci  are  closed  is  too 
easily  overlooked.  Errors  inherent  in  defects  of  technical  methods 
must  also  be  remembered.  Examination  for  bacilli,  simple  as  it  is, 
none  the  less  requires  a  certain  amount  of  experience.  I  saw  a 
patient  with  syphilitic  antecedents  suffering  from  manifest  pulmo- 
nary tuberculosis.  The  physical  signs  left  no  doubt  whatever  as 
to  the  diagnosis.  He  had  been  given  for  several  weeks,  and  to  his 
detriment,  large  doses  of  potassium  iodide.  His  physician,  a  very 
able  man,  who  had  instituted  the  treatment,  had  based  it  upon 
the  absence  of  Koch's  bacillus  in  the  expectorations.  There  had 
certainly  been  some  technical  error,  for  when  I  examined  the  case  I 
found  the  sputa  nummular  and  swarming  with  tubercle  bacilli. 
Such  errors  are  not  rare.  I  could  cite  several  examples  of  a 
similar  character. 

When  the  bacilli  are  present,  certainty  is  established.  When, 
however,  the  parasites  are  few  in  number,  doubt  still  remains.  We 
know  that  Koch's  bacillus  may  vegetate  upon  certain  mucous  mem- 
branes as  an  inoffensive  parasite.  Its  presence  does  not  necessarily 
imply  the  existence  of  a  tubercular  lesion.  Such  is  the  case  with 
the  tonsil,  which  often  contains  bacilli,  but  is  seldom  affected  by 
them.     The  difficulties  are  far  more  considerable  when  less  clearly 


DIAGNOSIS  AND  PROGNOSIS  OF  TNFECTI0U8  DISEASES.    609 

specified  bacteria  are  Looked  for.     For  example,  expectoration    are 
examined  and  streptococcus,  pneumococcui .  Friedlander'    bacilli]  . 

tetragenes,  ;i,ihI  various  spirilla  are  found.  Whal  righl  have  we  to 
conclude  that  such  and  such  a  microbe,  to  the  exclusion  of  other  . 
is  the  cause  of  the  morbid  manifestations?  [f  one  pecie  pre 
dominates,  the  probabilities  are  thai  ii  is  tin-  pathogenic  agent. 
There  is,  however,  no  absolute  certainty,  and  we  have  already  -ecu. 
with  reference  to  anginas,  how  difficull  interpretation  is  in  the 
majority  of  cases.  Thus,  in  chancriform  tonsillitis  an  a  sociation  oi 
spirilla  and  fusiforin  bacilli,  which  are  of  greal  diagnostic  value,  are 
found  The  same  association,  however,  may  be  me1  with  in  other 
clinical  types  and  even  in  syphilis.  Such  was  manifestly  the  case 
with  secondary  tonsillar  lesions  of  very  difficull  diagno 

When  bacteria  are  found  irregularly  disseminated  ;i  decision  Lb 
impossible.  Hence,  for  the  diagnosis  of  anginas,  another  procedure 
is  resorted  to — cultivation.  The  point  to  he  settled  is,  in  general, 
whether  an  angina  is  or  is  not  diphtheritic  in  nature.  A-  Loeffler's 
bacillus  rapidly  vegetates  in  gelatine  serum  and  develops  in  this 
medium  sooner  than  other  bacteria,  the  method  becomes  very 
simple.  A  particle  of  the  suspicious  exudate  is  spread  upon  gelatine 
serum  and  is  placed  in  the  incubator.  At  the  end  of  twelve  hours 
the  bacillus  of  Loeffler,  if  present,  produces  colonies.  This  mode  of 
action  is  usually  not  objectionable.  It  must  be  noted,  however, 
that  in  certain  cases  the  development  of  the  bacillus  is  more  tardy. 
It  sometimes  takes  twenty-four  or  thirty-six  hours.  On  the  other 
hand,  while  there  is  no  doubt  when  the  colonies  are  abundant  and 
rich  in  bacilli,  it  may  still  be  a  question  whether  an  angina  should 
necessarily  be  regarded  as  diphtheritic  simply  because  Loeffler's 
bacillus  has  been  detected  by  serum  culture.  If  another  medium 
had  been  employed,  a  different  result  would  have  been  obtained. 
If,  for  instance,  the  cultivation  had  been  made  in  bouillon  the 
streptococcus  might  be  present  and  Loeffler's  bacillus  absent.  What 
right,  then,  have  we  to  conclude  that  the  angina  was  diphtheritic? 
Why  should  the  results  furnished  by  cultivation  in  one  medium  be 
more  valuable  than  those  obtained  in  another?  Why  prefer  serum 
to  agar-agar  or  to  bouillon?  Why  accept  Loeffler's  bacillus  and 
ignore  the  streptococcus,  which  is  just  as  harmful? 

An  attempt  has  been  made  to  avoid  the  difficulty  by  the  admission 
of  a  hybrid  form  having  particular  clinical  characters,  which  has 
been    designated   strepto-diphtheria.      This   reasoning   is   open   to 

39 


(310  INFECTIOUS  DISEASES. 

criticism.  In  order  to  admit  this  form  the  development  of  two 
bacteria  in  blood  serum  is  required.  It  is  hard  to  conceive  why 
an  important  role  is  attributed  to  the  streptococcus  solely  on  the 
ground  that  it  develops  in  serum.  Its  multiplication  in  this  medium 
does  not  at  all  prove  its  virulence.  Even  though  we  admit  that  the1 
procedure  is  exact,  other  difficulties  arise.  What  conclusion  is  to 
be  drawn  in  those  cases  in  which  cultivation  gives  only  scanty 
colonies  of  the  diphtheria  bacillus?  It  is  known  that  this  bacillus 
quite  often  vegetates  in  the  normal  mouth.  When  it  is  encountered 
in  culture  it  may  be  asked  whether  or  not  we  have  to  deal  with  an 
inoffensive  parasite.  Moreover,  although  this  bacillus  is  readily 
recognized,  there  is  a  short  bacillus,  the  nature  of  which  is  in  no 
wise  determined  as  yet,  which  is  considered  by  some  as  a  variety 
of  the  diphtheritic  bacillus,  and  by  others  as  a  particular  microbe. 
In  this  case,  bacteriological  diagnosis  is  indecisive. 

Referring  to  the  results  which  we  have  described  in  treating  of 
microbic  associations  (p.  145),  it  may  be  noted  that  in  thirty-one 
cases  of  anginas  studied  comparatively  by  direct  examination  and 
by  cultivation  in  agar-agar  and  serum,  we  constantly  found  Loefner's 
bacillus  in  the  last-named  medium,  while  we  detected  it  in  only  half 
of  the  cases  by  direct  examination  or  by  cultivation  in  agar-agar. 
Moreover,  in  these  thirty-one  patients  the  exudate  contained  strepto- 
cocci visible  by  direct  examination  nine  times;  cultivation  in  agar- 
agar  revealed  them  sixteen  times,  and  cultivation  in  serum  three 
times  only*.  Still,  in  one  case  in  which  the  streptococcus  developed 
in  serum,  agar-agar  showed  only  the  tetragenus. 

These  reflections  are  by  no  means  intended  to  discredit  the  results 
furnished  by  bacteriology.  They  are  intended  only  to  call  attention 
to  the  disposition  of  many  authors  to  attribute  an  absolute  value  to 
the  data  of  cultivation.  A  vast  amount  of  research  is  yet  required 
in  order  to  base  a  description  of  anginas  upon  a  parallel  study  of 
their  clinical  aspect  and  experimental  results.  I  have  dwelt  upon 
anginas  because  these  are  the  affections  the  study  of  which  has 
most  profited  by  modern  bacteriological  investigations.  We  possess 
no  selective  medium  analogous  to  blood  serum  for  the  other  patho- 
genic bacteria.  The  preparation  of  media  for  the  cultivation  of 
specific  bacteria  in  the  midst  of  common  parasites  has  not  given 
gratifying  results. 

The  employment  of  peptone-water  is  useful  in  the  diagnosis  of 
cholera,  but  the  detection  of   Eberth's  bacillus  in  fecal  matters  is 


DIAGNOSIS  AND  PBOONOSIS  OF  INFECTIOUS  DISEASES.    r,\\ 

far  more  difficult.     Eisner's  formula  does  not  seem  to  respond  to 
the  purpose  in  view . 

Bacteriological  examination  ii  of  con  iderable  intere  I  in  connection 
with  sexual  diseases.  Examination  for  the  gonococcu  i  daily 
practised  and  serves  bo  establish  the  diagnosis  of  gonorrhea 
well  to  remark,  however,  thai  recently  there  have  been  found  in 
the  suppurations  of  the  genital  organs  anaerobic  microbes  which 
have  nothing  in  common  with  the  gonococcus,  bu1  ii  i  very  difficult 
to  recognize  them  by  a  simple  microscopic  examination. 

When  the  process  is  one  of  common  suppuration  two  casee  are 
possible:  The  focus  ui;iy  be  closed  or  open.  When  ii  i  closed  a 
puncture  is  made  into  it  and  a  specimen  of  the  Quid  i-  submitted 
to  microscopic  examination  and  to  cultivation.  The  data  ob- 
tained have  undeniable  value,  provided  the  resulte  of  direcl 
animation  be  carefully  compared  with  those  furnished  by  cultivation. 
If  by  both  of  these  procedures  a  single  species  is  found,  certainty 
is  almost  absolute,  but  not  complete,  since  it  is  possible  that  the 
true  pathogenic  agent  may  be  unrecognizable  by  our  present  methods 
of  staining  and  cultivation.  This  possibility  is  becoming  less  and 
less  as  bacteriology  advances,  and  the  result  is  perfect  in  most  cases. 
The  result  is  also  satisfactory  when  several  specie-  of  microbes  are 
found.  If,  however,  a  great  number  of  different  bacteria  are  re- 
vealed by  microscopic  examination,  and  if  cultivation  shows  only 
one  or  two,  the  difficulties  are  the  same  as  in  the  case  of  angina. 
Such  is  the  case  with  gangrenous  foci.  Anaerobic  cultures  have 
greatly  aided  the  study  of  this  morbid  process,  but  by  a  natural 
reaction  too  much  importance  has  been  attributed  to  anaerobics. 
In  most  cases  putrefactive  microbes  do  no  more  than  complete 
the  work  already  begun.  The}'  putrefy  tissues  altered  by  other 
microbes,  and  notably  by  aerobics.  Moreover,  we  must  remember 
that  the  latter  may  of  themselves  produce  certain  gangrenes  which 
are  sometimes  of  benign  character. 

When  an  open  focus  is  examined  the  results  are  very  clear  it  only 
one  species  of  microbe  is  found.  If  several  species  are  detected. 
the  difficulties  of  interpretation  are  the  same  as  in  the  case  of  angina. 
In  some  cases,  however,  the  presence  of  certain  morphological 
elements  is  of  paramount  importance.  Thus,  whether  the  lesion  be 
open  or  closed,  the  presence  of  yellow  grains  resembling  flowers  of 
sulphur  establishes  the  diagnosis  of  actinomycosis. 

The  associated  microbes  are  then  of  little  consequence :  the  nature 


612  INFECTIOUS  DISEASES. 

of  the  lesion  is  well  determined,  and  furnishes  accurate  indications 
for  treatment. 

The  microbe  may  likewise  be  looked  for  in  fluids,  secretions,  or 
natural  excretions,  or  even  in  the  organs.  In  this  connection  the 
blood,  urine,  fecal  matters,  and  cerebrospinal  fluid  are  examined. 
Capillary  punctures  into  the  viscera  are  practised,  particularly  into 
the  spleen.  By  microscopic  examination  of  the  blood  it  is  possible 
to  recognize  certain  absolutely  characteristic  specific  parasites,  such 
as  the  spirilla  of  recurrent  fever  and  the  hematozoon  of  malaria. 
The  search  for  the  hematozoon  is  not  always  easy,  but  when  it  is 
positive  the  result  has  considerable  importance  from  a  practical 
standpoint.  It  permits  elimination  of  symptomatic  intermittent 
fevers  and  gives  a  solid  basis  for  treatment.  As  we  have  already 
stated,  special  corpuscles  are  found  in  the  blood  of  variola  patients 
by  simple  microscopic  examination.  These  corpuscles  are  particu- 
larly numerous  in  the  hemorrhagic  form.  In  the  suppurative  forms 
they  are  seen  at  the  beginning  of  the  disease,  at  the  period  when 
diagnosis  is  difficult.  In  most  bacterial  diseases  microscopic 
examination  reveals  no  bacteria  or  reveals  them  only  at  a  more 
advanced  stage  when  death  is  approaching.  In  the  case  of  anthrax 
and  of  septicemias  the  blood  is  not  invaded  until  death  is  near. 
It  is  not  so,  however,  with  methods  of  cultivation,  which  may  give 
positive  results  at  a  less  advanced  period  of  an  infection,  provided 
cultivations  be  practised  on  a  large  scale.  According  to  the  pro- 
cedure employed  by  Davaine,  1  c.c.  of  blood  must  be  taken  from 
a  vein  and  placed  in  appropriate  media. 

Examination  for  microbes  in  the  urine  is  seldom  practised.  It 
is  a  difficult  procedure.  If  a  simple  microscopic  examination  is  to 
be  made,  the  urine  must  be  centrifuged  and  the  deposit  examined. 
If  cultures  are  to  be  made,  the  urine  must  be  drawn  by  aseptic 
catheterization,  which  requires  a  great  deal  of  practical  experience 
in  order  not  to  be  misled  by  accidental  contamination.  The  study 
of  fecal  matters  is  not  less  difficult.  In  certain  cases,  however, 
microscopic  examination  renders  service  by  showing  a  common 
microbe  predominating  or  by  revealing  a  .specific  agent.  Thus,  the 
tubercle  bacillus  may  be  found  in  the  excrements,  and  this  fact  is 
of  great  importance,  since  bacilli  which  have  been  ingested  do  not 
pass  into  the  fecal  matters.  The  presence  of  Koch's  bacillus  in  the 
feces,  then,  permits  affirmation  of  the  existence  of  intestinal  tuber- 
culosis.    In   dysentery  examination  of   the   dejecta   it   is    likewise 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES.    613 

necessary,  for  it  enables  us  to  determine  whether  or  nol  the  ci 

one  of  amebic  dysentery. 

In  recent  years  the  search  for  microbe  is  Hi"  cerebral  spinal 
fluid  has  acquired  great  importance.  Lumbar  puncture  being  an 
inoffensive  operation,  we  easily  conceive  how  serviceable  tlii-  method 

of  exploration  may  prove    The  search  for  microbe    m  the  0T( 
requires  greater  precautions.     Puncture  of  the  liver,  once  quite 
frequently  practised  for  the  diagnosis  "I'  typhoid  fever    us  rather 
an  uncertain  method,  .■mil  '•.■m  hardly  enter  into  '•uncut  practice. 

Inoculations  from  a  Diagnostic  Standpoint.  The  difficulty  oi 
attributing  morbid  manifestations  i<>  one  form  of  pathogenic  bacteria 
rather  than  i<>  another  has  suggested  the  method  of  inoculation  into 
animals.  It  was  even  hoped  that  this  method  would  enable  us  to  give 
a  positive  prognosis.  It  was  thought  that  a  relation  existed  between 
the  evolution  observed  in  man  and  the  effects  produced  by  experi- 
mental inoculation.  Such  a  relation  undoubtedly  existfi  in  a  certain 
number  of  cases,  but  not  in  all.  As  regards  the  streptococcus 
particularly,  the  results  are  absolutely  deceiving.  Cultures  pre- 
pared with  blood  taken  immediately  after  death  have  often  been 
injected  in  large  doses  without  producing  the  slightest  disturbance. 
Among  observations  which  I  have  collected,  the  following  may  be 
cited.  1.  Pulmonary  gangrene  ending  fatally;  the  fluid  contained 
in  the  lungs  presented  especially  streptococci.  When  directly 
inoculated  into  the  veins  of  a  rabbit  in  the  dose  of  1  cubic  centimetre, 
it  produced  a  chronic  disease  characterized  by  paraplegia  and  reten- 
tion of  urine,  ending  fatally  at  the  end  of  two  months.  The  cultures 
injected  into  the  veins  in  the  dose  of  5  c.c.  gave  rise  to  no  disorder. 
2.  Streptococcus  obtained  from  a  newborn  which  had  succumbed  to 
erysipelas  of  the  navel;  the  first  culture,  when  injected  into  two 
rabbits  in  the  dose  of  5  c.c,  caused  no  morbid  manifestations.  3. 
Streptococcus  obtained  from  an  aged  man  dead  of  erysipelas ;  same 
experiments,  same  results.  4.  Streptococcus  obtained  from  dead 
of  puerperal  fever;  same  experiments,  same  results.  These  few 
facts  once  more  demonstrate  how  difficult  it  is  to  apply  to  man 
conclusions  drawn  from  experiments  performed  upon  animals,  and 
how  uncertain  is  determination  of  virulence,  at  least  in  the  case  of 
the  streptococcus. 

It  is  true  that  a  great  number  of  observations  have  been  published 
which  seem  to  establish  that,  in  cases  of  angina,  inoculation  into 
animals  may  furnish  interesting  data.     For  example,  when  we  find 


614  INFECTIOUS  DISEASES. 

a  bacillus  presenting  the  characters  of  the  diphtheria  bacillus,  the 
nature  of  which  is  not  quite  well  determined,  it  is  incontestable  that 
inoculation  may  elucidate  the  problem.  Thus,  at  the  necropsy  of 
a  diphtheritic  case,  I  found  an  hepatic  abscess  containing  a  bacillus 
analogous  to  Loeffler's.  In  order  to  establish  a  more  certain  diag- 
nosis, I  inoculated  two  guinea-pigs.  One  was  kept  as  control  and 
rapidly  succumbed;  the  other,  which  received  at  the  same  time 
antidiphtheritic  serum,  remained  in  good  health.  In  this  instance 
the  demonstration  is  unassailable. 

AYhile  inoculation  solves  the  problem  when  a  single  species  of 
bacterium  is  detected  in  a  focus,  it  may  furnish  doubtful  data  when 
several  species  of  microbes  are  encountered.  If  one  of  these  is 
inoculated  and  found  to  be  pathogenic,  it  cannot  be  concluded  that 
it  was  the  cause  of  the  accidents,  for  the  agents  unconsidered  were 
perhaps  just  as  virulent.  Therefore,  in  order  to  form  a  conclusion, 
it  is  necessary  to  inoculate  all  the  microbes  isolated — a  task  repre- 
senting considerable  labor — and  still  the  result  would  be  disputable, 
for  the  reason  that  it  is  possible  that  the  specific  microbe  will  not 
develop  in  the  particular  medium  employed,  either  because  this 
medium  is  not  favorable  for  it  or  because  the  other  bacteria  prevent 
its  multiplication.  I  recognize,  however,  that  inoculation  into 
animals  may  be  of  very  great  service.  For  example,  a  polymicrobic 
culture  is  obtained.  By  injecting  it  into  an  animal  we  may  see  a 
bacterium  predominate,  and  it  will  then  be  possible  to  obtain  a  pure 
culture  after  one  or  two  passages  through  animals.  Of  course,  it 
would  not  yet  be  safe  to  draw  an  absolute  conclusion.  Nothing 
proves  that  the  microbe  which  is  the  most  harmful  for  the  animal 
was  the  one  most  harmful  for  man.  Here,  therefore,  is  a  method 
that  renders  remarkable  service  to  the  experimenter  rather  than  to 
the  clinician.  Confining  ourselves  to  the  domain  of  clinical  diagnosis, 
we  find  various  infections  the  diagnosis  of  which  may  be  facilitated 
by  inoculation.  These  are  the  pneumococcic  infections,  anthrax, 
glanders,  tuberculosis,  hydrophobia,  and,  less  frequently,  gaseous 
gangrene  and  tetanus. 

When  the  pneumococcic  nature  of  a  lesion  is  suspected,  an  inocu- 
lation is  made  into  the  mouse.  The  animal  succumbs  within  twenty- 
four  or  forty-eight  hours,  and  examination  of  the  blood  shows 
characteristic  capsulated  diplocojcci.  It  is  well  to  remember,  how- 
ever, that  this  bacterium  is  often  encountered  in  the  saliva  of  healthy 
individuals.     The  positive  result  of  this  inoculation  cannot,  there- 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DI8EA8E8.    616 

fore,  lead  to  an  unquestionable  conclusion.     When  ;i  lesion  i 
pected  to  be  of  anthrax,  diagnosis  may  be  a  matter  of  difficulty,  for 
the  reason  thai  malignanl  pustule  often  contains  very  few  bacteria, 
and,  therefore,  experimental  inoculation  i    negative. 

[n  a  case  in  which  the  diagnosis  was  difficull  and  which  terminated 
in  recovery  I  inoculated  four  guinea-pigs  with  the  serum  of  the 
vesicles.  ( >ne  of  these  animals  died  of  anthrax,  thus  demonstrating 
the  nature  of  the  lesion  which,  without  inoculation,  mighl  have  Ween 
interpreted  in  a  differenl  manner. 

The  diagnosis  of  glanders  often  presents  greal  difficulties.  An 
experimental  method  has,  therefore,  been  long  looked  for.  The  ase 
first  served  for  purposes  of  experimentation.  When  this  animal  is 
employed  (lie  operation  is  performed  in  the  following  manner: 
After  shaving  the  forehead,  cutaneous  scarifications  are  made,  and 
then  the  suspicious  pus  is  rubbed  upon  them.  From  the  tenth  to 
the  fourteenth  day  the  general  phenomena  appear,  and  the  animal 
soon  dies  of  bronchopneumonia.  The  necropsy  reveals  glanders 
granulations  in  the  viscera.  Instead  of  the  ass  the  dog  may  be 
employed.  The  same  method  is  resorted  to,  and  four  or  five  day- 
after  inoculation  a  glanders  ulcer  appears  which  subsequently  heals. 
Christot  and  Kiener  proposed  a  simpler  procedure.  They  advised 
inoculation  into  the  guinea-pig.  The  animal  died  in  eight  or  ten 
days  with  characteristic  lesions.  The  best  method  is  that  of  Straus. 
The  suspicious  pus  is  injected  into  the  peritoneum  of  a  male  guinea- 
pig.  At  the  end  of  forty-eight  hours  a  testicular  vaginalitis  develops. 
The  skin  of  the  scrotum  becomes  red  and  the  two  layers  of  the  tunica 
vaginalis  adhere  by  a  purulent  exudate.  The  testicle  and  epididymis 
are  seldom  involved.  This  method  is  good,  but  not  perfect.  The 
pus  may  contain  various  bacteria  capable  of  producing  a  fatal  peri- 
toneal septicemia.  Hence,  it  is  advisable  to  inoculate  two  guinea- 
pigs,  one  beneath  the  skin,  the  other  into  the  peritoneum.  On  the 
other  hand,  various  pyogenic  microbes  behave  like  the  bacillus  of 
glanders  (Nocard).  The  result  of  inoculation  must,  therefore,  be 
controlled  by  bacteriological  examination  and  cultivation. 

Examination  for  the  tubercle  bacillus  is  so  easy  that  inoculation 
is  seldom  necessary.  In  cases  of  local  tuberculosis,  however,  and 
in  those  pulmonary  lesions  in  which  favorable  evolution  seems  to 
remove  all  suspicions  as  to  the  tubercular  nature  of  the  process,  as 
well  as  in  pleuritic  effusions,  the  bacilli  are  so  few  in  number  that 
there  is  great  danger  of  not  detecting  them  by  microscopic  exami- 


(316  ISFECTIO  US  DISEA SES. 

nation.  In  such  instances  inoculation  is  most  serviceable.  The 
inoculation  must  be  practised  upon  the  guinea-pig,  which  is  the 
animal  most  sensitive  to  tuberculosis.  Survival  is  very  long;  it 
often  exceeds  rive  or  six  weeks,  and  at  times  the  animal  may  live 
for  several  months  or  even  a  year.  The  early  development  of 
adenopathies  is  significant.  Six  or  eight  days  after  inoculation  the 
lymphatic  glands  corresponding  to  the  point  of  inoculation  become 
congested,  and  other  glands  are  later  involved.  These  multiple  and 
progressive  glandular  affections  are  absolutely  characteristic.  The 
method  may,  therefore,  be  of  use,  notably  in  cases  of  serous  pleurisy. 
As  is  known,  the  diagnosis  of  hydrophobia  is  a  matter  of  great 
difficulty.  Even  at  the  necropsy  a  retrospective  diagnosis  cannot 
be  made.  No  characteristic  lesion  is  found  in  the  viscera  and  tissues. 
This  fact  is  of  considerable  importance  in  practice.  When  an 
individual  is  bitten  by  a  rabid  dog  it  is  too  often  the  custom  to  kill 
the  animal  and  then  send  the  cadaver  to  a  veterinary  physician  for 
necropsy.  Great  diagnostic  value  was  formerly  attached  to  the 
presence  of  foreign  bodies  in  the  stomach  of  rabid  dogs.  These 
animals  bite  and  swallow  anything  they  encounter.  Hence,  sub- 
stances which  are  not  usually  among  the  contents  of  this  organ, 
such  as  pieces  of  wood,  straw,  earth  and  gravel,  are  found  in  their 
stomachs.  It  has  been  demonstrated,  however,  that  these  findings 
are  of  no  diagnostic  importance.  Such  substances  are  likewise 
found  in  non-hydrophobic  dogs.  In  view  of  the  investigations  of 
Van  Gehuchten,  histological  examination  may,  perhaps,  give  better 
results.  But  such  researches  are  delicate  and  require  accurate 
knowledge  of  histology.  For  the  time  being  the  study  of  symptoms 
seems  to  me  to  be  of  greater  importance.  Hence,  this  practical 
conclusion:  No  dog  which  has  bitten  a  person  should  be  killed: 
but  it  should  be  confined  and  carefully  observed.  This  is  the  only 
means  of  learning  at  the  end  of  two  or  three  days  whether  it  is 
hydrophobic  or  not.  Moreover,  the  circumstances  under  which  the 
biting  occurs  furnishes  a  presumptive  basis.  It  may  be  said  that  a 
dog  which  bites  without  provocation  and  without  any  appreciable 
cause  is  generally  rabid.  If  the  animal  has  been  killed,  the  only 
means  of  obtaining  conclusive  information  is  inoculation.  This 
operation  is  generally  performed  upon  the  rabbit.  The  emulsion 
obtained  with  the  medulla  is  injected  beneath  the  dura  mater.  The 
operation  is  extremely  simple:  The  animal  being  firmly  bound, 
and,  if  necessary  anesthetized,  an  incision  is  made  into  the  skin. 


DIAGNOSIS  AND  PB0ON0SI8  OF  INFECTIOUS  DISEASES,     617 

The  cranium  is  opened  by  means  of  a  smal  trepan,  avoiding  the 
upper  Longitudinal  sinus.  The  hemorrhage  produced  by  incision  ol 
the  bone  is  generally  quickly  arrested.  Then,  by  meane  oi  a  curved 
canula  adjusted  to  a  Pravaz  syringe,  the  dura  mater  i  punctured 
and  a  few  drops  of  the  emulsion  are  injected  beneath  this  membrane. 
The  canula  is  withdrawn,  the  wound  sutured  and  covered  with 
iodoform  collodion.  Under  these  conditions  the  animal  contract* 
hydrophobia  after  a  period  of  incubation  varying  from  twelve  to 
fifteen  days.    T<>  ensure  the  production  of  hydrophobia,  il  U  oo1 

absolutely    neeess:ir\     lo    resorl     I"    llie    procedure    jusl     described. 

Introduction  of  the  virus  into  the  anterior  chamber  of  the  eye  gives 

nearly  as  certain  results.  The  same  is  true  when  the  inoculation  i- 
made  into  any  nerve  whatever,  for  example,  into  a  peripheral  nerve. 
Galtier,  l)i  Vesica  and  Zagari  have  shown  thai  the  sciatic  nerve 
offers  a  very  reliable  route  of  introduction.  Finally,  when  .1  con- 
tused wound  contaminated  by  foreign  bodies  or  earth  becomes  the 
starting  point  of  morbid  manifestations,  the  inoculation  into  a 
guinea-pig  of  the  fluid  discharged  from  the  lesion  or,  still  better,  of  a 
particle  obtained  by  scraping,  may  reveal,  within  forty-eighl  hour.-. 
the  presence  of  the  microbe  of  gaseous  gangrene  or  of  tetanus. 

Cytologic  Examination.  A  new  method  of  diagnosis  consist-  in 
searching  for  certain  reactions  produced  in  the  organism  by  patho- 
genic agents.  The  attention  of  observers  was  first  attracted  by  the 
blood.  In  fact,  from  the  start  of  infections  this  fluid  undergoes 
profound  modifications,  some  of  which  bear  upon  the  cellular  elements 
and  may  be  detected  under  the  microscope.  We  have  already  stated 
that  the  variations  in  the  white  blood  corpuscles  enable  us  to  follow 
the  evolution  of  infections,  and  at  times  to  foretell  their  course  and 
announce  relapses.  These  observations  less  frequently  serve  the 
purposes  of  diagnosis.  Nevertheless,  the  researches  of  Courment 
and  Montagard  and  those  pursued  at  the  same  time  by  Dr.  "Weil 
in  our  wards  show  that  the  leucocytic  formula  of  the  blood  presents 
particular  characters  in  variola.  The  results  are  so  clear  that  we 
often  resort  to  this  procedure  in  order  to  settle  diagnostic  difficulties. 
It  must  be  remembered,  however,  that  varicella  and  variola  produce 
analogous  modifications  in  the  blood.  The  method  mostly  serves 
to  differentiate  variola  from  other  eruptive  fevers  and  various 
pyogenic  infections  which  simulate  it. 

The  examination  of  the  cells  may  be  made  not  only  in  the  blood 
but  in  other  fluids  and  exudates.     Examination  of  the  cerebro- 


618  /  SFECTIO  US  DISEA  SES. 

spinal  fluid  and  of  effusions  produced  in  various  serous  membranes 
has  led  to  a  cyto-diagnosis  the  importance  of  which  lias  been  well 
shown  by  Widal  and  Ravaut. 

In  cases  of  primary  tuberculosis  of  the  pleura  pleuritic  effusion  is 
remarkable  for  the  almost  exclusive  presence  of  small  lymphocytes. 
In  individuals  afflicted  with  cancerous  or  ulcerating  lesions  of  the 
lungs,  or  hydropneumothorax,  numerous  altered  polynuclears  are 
found,  while  in  mechanical  pleurisy  the  endothelial  cells  of  the 
pleura  predominate.  In  the  case  of  streptococcic  pleurisy  neutro- 
philic polynuclears  are  almost  exclusively  present.  In  pneumo- 
coccic  pleurisy  the  greater  part  of  the  cells  is  represented  by  poly- 
nuclears and  large  mononuclear  cells  mixed  with  red  blood  corpuscles 
and  a  few  lymphocytes. 

The  Vesicatory  Test.  These  researches  are  applicable  only  to 
certain  special  cases.  Hence,  it  seemed  to  me  to  be  interesting  to 
determine  the  cytologic  formula  of  effusions  which  may  be  produced 
in  man  by  the  application  of  vesicatories.  The  examinations  which 
we  made  with  Dr.  Josue1  established  that  the  vesicle  produced  by  a 
vesicatory  holds  in  suspension  a  fairly  large  number  of  cells.  In 
the  normal  man  a  strong  proportion  of  polynuclear  eosinophiles  is 
found.  In  individuals  suffering  from  an  infectious  disease  these 
cells  are  less  numerous  or  altogether  absent.  They  reappear  if  the 
organism  overcomes  the  infection.  The  vesicatory  test  thus  furnishes 
valuable  indications  regarding  the  intensity  of  the  toxi-infectious 
impregnation  of  the  organism  and  the  mode  of  reaction  of  the 
hematopoietic  organs.  It  is  readily  conceivable  what  advantage 
may  be  drawn  from  such  information  from  a  diagnostic  and  especially 
prognostic  standpoint.  The  difference  in  the  results  obtained  in  the 
healthy  man  and  in  the  sick  must  depend  upon  the  action  exercised 
by  microbic  toxins  upon  the  hematopoietic  organs,  and  notably  upon 
the  bone-marrow.  Under  the  influence  of  these  poisons  the  bone- 
marrow  gives  rise  to  neutrophilic  polynuclears.  On  the  contrary, 
it  cannot  furnish  eosinophiles.  Ehrlich  has  well  shown  this  sort  of 
antagonism  which  exists  between  the  infectious  process  and  eosino- 
philia.  The  application  of  a  vesicatory  stimulates  the  production 
of  eosinophiles,  and  the  examination  of  the  fluid  shows  in  what 
measure  the  bone-marrow  is  capable  of  producing  these  elements. 
The  vesicatory  test  thus  enables  us  to  determine  the  intensity  of 

1  Roger  and  Josue\    L'epreuve  du  vesicatoire.    Soc.  m6d.  des  hopitaux,  May  3,  1901 . 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES.    619 

the  action  of  toxins  upon  the  hematopoietic  organs.  By  this  method 
we  may  judge  to  whal  extenl  the  function  of  the  e  organ  i-  dimin- 
ished under  the  influence  of  the  toxic  element. 

Apart  from  the  eosinophilic  polynuclear  there  are  found  in  the 
vesicle  neutrophilic  polynuclears  and  large  and  small  mononuclears. 
It  is  not  rare  to  find  in  the  preparations  a  certain  dumber  of  large 
mononuclear  elements  containing  granulations.  These  are  myelo- 
cytes. Tliis  fact  is  interesting,  since  no  such  cells  are  commonly 
found  in  the  Mood  or  in  pathological  exudates.  They  generally 
remain  in  the  bone-marrow,  where  they  give  rise  to  white  globules 
with  polymorphous  nuclei  or  polynuclears.  The  presence  of  myelo- 
cytes [troves  that  the  vesicatory  produces  a  very  profound  effecl 
upon  the  hematopoietic  organs.  Besides  the  cells  above  described, 
all  of  which  are  similar  to  those  circulating  in  the  normal  or  patho- 
logical blood,  particular  elements  are  found  in  the  fluid  produced  by 
the  vesicatory.  These  are  cells  provided  with  a  thin  layer  of  proto- 
plasm which  is  colored  brownish -yellow  by  triacid  and  rose  by  eosin. 
Their  nucleus,  which  is  round  or  oval,  is  stained  green  by  triacid  and 
pale  violet  by  hematoxylin,  but  is  not  clearly  defined.  Unable,  as 
yet,  to  decide  the  nature  and  origin  of  these  elements,  we  shall 
designate  them  "vesicatory  cells.''  Our  researches  were  made  upon 
two  normal  individuals  and  twenty-seven  patients,  eleven  of  the 
latter  suffering  from  pulmonary  tuberculosis,  and  three  seemingly 
from  tubercular  pleurisy.  The  technique  employed  was  very  simple. 
Twelve  hours  after  th  ;  application  of  a  vesicatory  of  four  or  five 
square  centimetres,  when  the  bulla  was  well  formed,  the  fluid  was 
taken,  centrifuged,  and  decanted,  and  the  sediment  spread  upon 
slides  and  dried  over  the  flame.  Most  of  the  preparations  fixed  by 
heat  at  230°  F.  (110°  C.)  were  stained  with  Ehrlich's  triacid  solution 
or  thionin.  A  few  were  treated  with  alcohol-ether  and  stained  with 
eosin-hematoxylin.  The  preparations  obtained  by  the  triacid  stain 
are  the  clearest. 

In  the  two  normal  individuals  we  found  a  very  large  proportion 

of  eosinophils.     In  no  pathological  case  did  we  find  such  a  great 

number.     A  count  of  the  various  species  of  cells  gave  the  following 

figures : 

i.  ii. 

Neutrophilic  polynuclears     ....    65.0  per  cent.  77. S  per  cent. 

Eosinophilic  polynuclears      ....    25.5     "        "  19.2 

Large  mononuclears 1.0     "        "i 

3  0      •  ■        " 
Small  mononuclears S.O     "        "J 

Vesicatorv  cells 0.5      "        "  0.0 


620  IXFECTIO  US  DISEA  SES. 

The  vesicatory  test  leads  to  altogether  different  results  in  tuber- 
culous subjects.  In  cases  of  common  chronic  tuberculosis  a  very 
great  number  of  polynuclears  are  found.  These  reach  or  exceed 
90  to  95  per  cent.  On  the  other  hand,  the  eosinophiles  are  very 
rare  and  in  most  cases  are  absent.  The  proportion  of  large  and 
small  mononuclears  is  quite  variable  according  to  the  case.  That 
of  the  vesicatory  cells  varies  between  0.5  and  3  per  cent.  In  one 
tubercular  case  (Obs.  XL)  the  number  of  the  eosinophiles  was  rela- 
tively large.  It  amounted  to  3.2  per  cent.  This  case  was  not  an 
exception  to  the  rule,  for  it  was  a  man  suffering  from  a  peritoneal 
localization  and  from  pulmonary  lesions  tending  toward  sclerosis. 
The  relatively  high  percentage  of  eosionphiles  indicated  the  favor- 
able course  of  the  disease  toward  recovery. 

Furthermore,  we  have  noticed  that  the  cells  present  a  special 
aspect  in  tuberculous  individuals.  They  are  swollen  and  much 
larger  than  in  normal  subjects.  This  particular  state  of  the  cellular 
elements  is  not  absolutely  peculiar  to  tuberculosis,  but  it  is  far  more 
pronounced  in  this  infection  than  in  others.  Hence,  when  it  is 
manifest,  it  may  lead  to  the  detection  of  a  latent  tuberculosis. 
This  is  precisely  what  happened  in  one  of  our  cases  (Obs.  XII.). 
Having  applied  a  vesicatory  to  a  man  whom  we  considered  to  be 
in  normal  condition,  we  were  surprised  to  find  in  the  fluid  a  low 
percentage  of  eosinophiles  as  compared  to  the  normal  ratio,  and  a 
sufficiently  great  number  of  swollen  cells.  Minute  examination  of 
the  respiratory  organs  enabled  us  to  recognize  slight  but  incontest- 
able lesions,  which,  until  then,  had  produced  no  functional  disturb- 
ance. Percussion  revealed  dulness  under  the  right  clavicle  and  in 
the  left  supraspinous  region.  In  the  same  regions  inspiration  was 
harsh  and  attended  by  a  few  dry  rales  and  pleuritic  frictions.  The 
relatively  high  percentage  of  eosinophiles  (7.82  per  cent)  indicated 
that  the  constitution  was  vigorous — a  fact  quite  in  harmony  with 
the  results  of  clinical  examination.  It  may  be  added  that  the 
vesicatory  test  gives  the  most  valuable  information  in  the  beginning 
of  tuberculosis  and  enables  us  to  appreciate  the  degree  of  resistance 
of  the  individual  and  his  chances  of  recovery. 

The  number  of  eosinophiles  was  still  larger  in  two  cases  of  acute 
serofibrinous  pleurisy.  This  affection  may  be  considered  as  a  local 
tuberculosis  of  the  pleura  tending  toward  recovery.  It  would, 
therefore,  be  natural  to  expect  to  find  a  formula  expressing  the 
resistance  of  the  organism.     This  is  precisely  what  was  found  in 


DIAGNOSIS  AND  PROGNOSIS  OF  XNFE0TI0U8  DISEASES      821 

Observations  XIII.  and  XIV.  [n  a  third  case,  however  (Ob  XV.  . 
the  formula  was  different.  This  wa  a  case  of  pleurisy  which  wb 
being  cured,  but  a  day  before  we  applied  Wk-  ve\  icatory  the  patienl 
was  attacked  by  intense  gastrointestinal  disorder  with  hypo- 
thermia 95.7°  V.  (MA0  C).  This  superadded  affection  ufficed  t<, 
completely  modify  the  cellular  formula  of  the  vesicatory  fluid.  Thk 
observation  established  the  extreme  sensitivenest  of  the  procedure 
and  shows  with  what  rapidity  pathologic  influences  affeel  the  organic 
reactions. 

TUBERCULOSIS. 


I. 

II. 

III. 

IV. 

V. 

1 
VI. 

VII. 

VIII. 

IX. 

X. 

XI. 

XII. 

I'l 
XIII 

XIV. 

XV. 

Neutrophilic             | 
polynuclears      j 

9.26 

85.5 

95.0 

96.0  91.6  98.6 

95.00 

89.25 

62 

90.0 

92.6 

74.10 

71.  1 

06.8    !'l." 

Eosinophilic              ) 
polynuclears      j 

0 

0 

0.8 

0       0 

0 

0 

0 

0 

0.8 

3.2 

7.32 

18.7 

17.0 

1.2 

Large  mononuclears 

3.4 

9.0 

1.0 

0       2.8 

0.8 

1.00 

5.75 

21 

2.0 

•j.  6 

3.64 

n.:. 

5.0 

Small  mononuclears 

2.8 

0 

1.8 

1.2    4.8 

0 

1.75 

0 

10 

5.2 

0.4 

13.14 

- 

1.5 

0 

Neutrophilic  mye-  1 
locytes               j 

0.8 

3.5 

0.3 

0 

0.8 

0.6 

0.75 

1.5 

7 

0.4 

0.8 

0.18    0 

1.2 

1.8 

Eosinophilic  mye-  ) 
locytes                j 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0.4 

0.36    0 

0.8 

0.2 

Vesicatory  cells 

0.4 

2.0 

1.0 

2.8 

0 

0 

1.5     3.5 

0 

1.6 

0 

0.76    1.2 

1.7 

0.4 

I.  Pulmonary  tuberculosis  at  the  third  stage. 

II.  Pulmonary  tuberculosis  at  the  third  stage. 

III.  Pulmonary  tuberculosis  at  the  third  stage. 

IV.  Pulmonary  tuberculosis  at  the  second  stage.     Infiltration  of 
the  entire  left  lung. 

V.  Pulmonary   tuberculosis   in    the    second   stage.     Generalized 
bronchitis. 

VI.  Pulmonary  tuberculosis  in  the  second  stage. 

VII.  Pulmonary  tuberculosis  in  the  second  stage.     Generalized 
bronchitis. 

VIII.  Pulmonary  tuberculosis  in  the  third  stage.    Intense  fever. 

IX.  Pulmonary  tuberculosis  in  the  third  stage.     Hemoptys  - 
Fever.     Erysipelas  cured  since  twenty-six  days.     (Notice  the  small 
number  of  neutrophilic  polynuclears  and  the  large  percentage  of  the 
mononuclears) . 

X.  Tubercular  pulmonary  congestion. 


622  IXFECTIO  US  DISEASES. 

XI.  Pulmonary  tuberculosis  with  fibrinous  evolution.  Tubercular 
peritonitis. 

XII.  Slight  pulmonary  tuberculosis.  Dulness  in  the  front  and 
right  side  of  the  chest  and  the  left  side  of  the  back ;  harsh  respiration : 
a  few  dry  rales  and  frictions.     Apyrexia. 

XIII.  Acute. serofibrinous  pleurisy. 

XIV.  Acute  serofibrinous  pleurisy  in  a  very  vigorous  man. 

XV.  Acute  serofibrinous  pleurisy  on  the  way  to  recovery.  Intense 
gastrointestinal  disturbances  and  hypothermia  since  the  previous 
day. 

In  erysipelas  the  eosinophils,  which  are  absent  when  the  disease 
is  at  the  stationary  period,  reappear  at  the  moment  of  recovery. 
These  elements,  however,  are  few  in  number  during  the  days  imme- 
diately following  the  morbid  termination.  The  organic  reactions 
which  are  profoundly  modified  by  the  infectious  attack,  remain 
disturbed  for  a  long  time.  At  the  same  time  that  the  percentage 
of  the  eosinophils  increases,  that  of  the  neutrophilic  polynuclears 
diminishes  at  the  end  of  the  disease.  The  mononuclears  are  also 
far  more  numerous  than  at  the  stationary  period. 

We  have  employed  the  vesicatory  test  in  two  cases  of  mumps  and 
one  of  acute  angina.  All  these  observations  concur  in  demonstrat- 
ing that  the  histological  examination  of  the  vesicatory  fluid  reveals 
the  mode  of  reaction  of  the  hematopoietic  organs  in  a  given  case. 
In  fact,  we  see  that  the  same  toxic  cause,  the  application  of  canthar- 
ides,  determines  the  presence  of  different  cells  in  the  vesicatory  fluid 
according  to  the  degree  of  intensity  of  the  infectious  impregnation, 
according  as  the  organism  resists  with  more  or  less  success,  and 
according  to  the  phases  of  the  struggle.  This  method  is  extremely 
sensitive.  A  superadded  or  even  slight  infection  suffices  to  com- 
pletely modify  the  results.  It  must,  however  be  remembered  that 
the  vesicatory  test  indicates  only  the  degree  of  intensity  of  infectious 
impregnation.  An  intense  infection  may  be  benign,  for  example, 
an  acute  angina.  A  slight  infection  may  be  more  serious,  even  if 
the  organism  resists,  for  example,  a  local  tuberculosis.  The  vesic- 
atory test  furnishes  data  concerning  not  the  absolute  prognosis  of 
the  infection,  but  the  degree  of  impregnation  of  the  organism. 
From  a  purely  theoretical  standpoint  it  is  interesting  to  remark 
how  an  infection,  though  benign  and  well  localized,  modifies  all  the 
organic  reactions.  A  catarrhal  angina  is  sufficient  to  disturb  the 
leucocytic  equilibrium  of  the  economy.     Under  these  conditions  the 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISE  I    E       623 

same  irritating  cause  produces  other  effect*  than  in  s  normal  indi- 
vidual. Our  investigations  thu  explain  why  econdary  Infection/ 
so  often  differ  in  their  mode  of  evolution  from  primary  infection  . 

Diagnosis  According  to  Chemical  Modifications  in  Fluids.  An 
infection  produces  no1  only  histological  bul  also  chemical  modifica- 
tions in  the  blood  and  fluids,  It  causes  notably  the  appearance  in 
the  serum  and  certain  exudates  of  substances  which  -•■••in  to  be 
intended  to  combal  infection.  Among  these  the  mosl  interesting 
from  a  diagnostic  standpoinl  is  thai  which  causes  agglutination  of 
the  microbes.  Everyone  is  well  acquainted  with  the  practical 
application  which  Dr.  Widal  has  made  of  this  in  the  diagnosis  of 
typhoid  fever.  The  procedure  is  quite  simple.  A  few  drops  of  fin- 
blood  of  the  patienl  are  taken,  and  then  the  serum,  diluted  in  a 
certain  proportion,  is  mixed  with  a  fresh  culture  of  Eberth's  typhoid 
bacillus.  If  the  case  is  one  of  typhoid  fever,  the  scattered  elements 
unite  in  small  masses.  This  method,  designated  as  the  "method  of 
serum-diagnosis,"  is  currently  employed  in  the  diagnosis  of  typhoid 
lover.  According  to  the  researches  of  Dr.  Arloing  and  his  disciples, 
this  method  is  applicable  also  to  tuberculosis.  Other  Bubstances 
which  arc  produced  in  the  blood  of  infected  subjects  may  Likewise 
serve  in  diagnosis. 

Among  the  secretions  only  one  is  commonly  studied  clinically, 
namely,  the  urine.  Its  examination  in  the  course  of  infectious  dis- 
eases is  of  great  importance,  but  it  is  more  interesting  for  progno>b 
than  diagnosis.  The  modifications  in  quantity  and  color,  the  varia- 
tions in  the  amount  of  cells  and  nitrogenous  substances,  the  appear- 
ance of  abnormal  substances,  such  as  albumin,  peptones,  and  glue*  ise, 
enable  us  to  appreciate  the  changes  occurring  in  the  organs  and  in 
general  nutrition,  but  do  not  help  us  to  determine  the  nature  of 
the  disease.  Likewise,  the  detection  of  biliary  pigments — urobilin— 
is  interesting  only  as  regard's  prognosis.  The  only  reaction  which 
sometimes  may  serve  for  diagnostic  purposes  is  Ehrlich's  diazo 
reaction.  Although  it  is  not  absolutely  a  specific,  this  reaction  is 
an  important  sign  in  the  diagnosis  of  typhoid  fever.  It  is  sometime  s 
manifest  as  early  as  the  third  or  fourth  day.  but  may  be  delayed 
until  the  beginning  of  the  second  week.  It  also  enables  us  to  fore- 
tell certain  complications.  If  it  suddenly  ceases  unattended  by 
concomitant  amelioration,  some  secondary  infection  or  a  renal  lesion 
must  be  suspected.  If  it  increases  in  intensity  it  means  an  aggrava- 
tion of  the  disease.     Its  reappearance  during  convalescence  indicates 


(324  IXFECTIO  US  DISEASES. 

a  relapse.  The  diazo  reaction  is  likewise  observed  in  typhus  fever, 
in  acute  tuberculosis,  pyemia,  septicemia,  measles,  scarlatina,  and 
at  times  in  pneumonia. 

Diagnosis  by  Therapeutics.  We  must  now  say  a  word  regarding 
the  influence  of  certain  substances  capable  of  modifying  the  evolution 
of  affections  and  thus  elucidating  their  character.  Such  are  specific 
medicines,  which  serve  to  determine,  as  the  case  may  be,  the  malarial 
or  syphilitic  nature  of  an  infection.  The  action  of  quinine  upon 
malaria  is  too  well  known  to  need  more  than  an  allusion.  Syphilis 
has  two  specifics:  salts  of  mercury  and  iodide  of  potassium.  The 
test  treatment  is  constantly  employed  in  the  diagnosis  of  difficult 
cases.  It  should  be  remembered,  however,  that  the  action  of  the 
iodides  is  exercised  in  the  same  manner  in  another  infection,  namely, 
actinomycosis.  The  specific  character  and  diagnostic  value  of  the 
iodides  thus  lose  much  of  their  importance.  It  is  even  likely  that 
many  cases  of  actinomycosis  have  been  mistaken  for  instances  of 
tertiary  syphilis. 

Diagnosis  by  Microbic  Toxins.  While  the  number  of  specifics 
drawn  from  the  inorganic  world  are  so  small  in  number,  it  is  hoped 
that  microbic  cultures  will  furnish  some  such  specifics.  This  hope 
is  founded  upon  the  investigations  of  Koch.  In  studying  the  effects 
of  tuberculin,  this  author  showed  that  the  reactions  differ  markedly 
according  as  this  extract  of  cultures  of  tubercle  bacilli  is  injected 
into  a  healthy  or  a  tubercular  individual.  At  the  end  of  four  to 
five  hours  after  the  injection  a  chill  occurs,  and  the  temperature 
rises  as  high  as  102.2°,  104°  F.  and  even  higher,  105.8°  F.  (39°,  40°  C. 
and  even  41°  C).  The  patient  feels  tired.  He  is  tortured  by  con- 
stant coughing,  has  at  times  nausea  and  vomiting.  He  experiences 
very  intense  pain  in  the  epigastrium,  extremities,  and  articulations. 
These  symptoms  last  from  twelve  to  fifteen  hours ;  but  may  be  pro- 
longed for  two  or  three  days,  or  be  followed  by  a  secondary  fever 
after  the  cessation  of  the  reaction,  depending  upon  infect  on  by  other 
microbes  (pneumococci,  staphylococci),  the  development  of  which  is 
favored  by  the  so-called  "lymph."  Coincidently  with  these  general 
disturbances  local  phenomena  in  the  tubercular  lesions  are  produced, 
which  may  readily  be  appreciated  by  observing  what  occurs  in  the 
case  of  lupus.  The  diseased  parts  swell  and  become  red.  Here  and 
there  they  become  brown  and  necrosed.  Two  or  three  days  later 
the  redness  diminishes  and  the  lesion  is  covered  with  yellowish  crusts 
formed  by  the  air-dried  serum.     Two  or  three  weeks  later  the  crusts 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES,    026 

become  detached,  and  in  favorable  ca  es  leave  •■•  cicatrix  of  good 
appearance.    Several  injections  are  generally  required  to  obtain  this 
result.    In  tuberculosis  of  the  lymphatic  glands,  as  well  a    ino 
and  articular  tuberculosis,  the  reactions  are  less  intense,  bul  they 

live,  always  percept  ible. 

It,  was,  therefore,  hoped  thai  the  so-called  "lymph"  would  i 
to  diagnose  tuberculosis,  and  thu  e  tablish  the  nature  of  at  uspicioui 
lesion  and  also  to  decide  whether  an  old  focue  was  really  cured. 
The  specific  value  of  tuberculin  is  notably  diminished  by  the  fad 
that  it  produces  intense  reactions  in  non-tubercular  cases,  for 
instance,  in  cases  of  cancel-,  sypli' lides,  scarlal  in;i,  gonorrheal  cystitis, 
leprosy,  and  actinomycosis.  Several  authors,  and  particularly  Maydl, 
have  observed  a  typical  reaction  in  healjbhy  individuals  who  had 
received  only  one  or  I  wo  milligrams  of  the  ' '  lymph.  "  On  the  other 
hand,  the  injection  does  nol  always  produce  reactions  in  tuberculous 
subjects.  Sometimes  the  general  phenomena,  and  sometimes  the 
local  manifestations,  are  lacking.  Furthermore,  various  substances, 
microbic  or  otherwise,  may  produce  in  tuberculous  individuals  dis- 
turbances similar  to  those  caused  by  tuberculin.  Injections  of 
artificial  serum  are  often  followed  by  marked  reactions,  and, 
shown  by  Hutinel,  these  may  be  utilized  for  diagnosis.  We  may. 
therefore,  conclude  that  Koch's  "lymph"  is  not  absolutely  specific. 
Other  substances  behave  in  the  same  manner,  and  it  does  not  act 
exclusively  upon  tubercular  lesions.  Nevertheless,  some  authors 
think  that  it  may  still  be  profitably  employed  at  least  in  animals. 
German  veterinarians  who  have  studied  its  action  upon  tubercular 
cows  have  obtained  reactions  with  doses  of  3  to  10  centigrams,  which 
produce  no  disturbance  whatever  in  healthy  cows. 

Mallein.     The  discovery  of  tuberculin  by  Koch  led  bacteriologists 
to  search  for  analogous  substances  in  other  cultures.    Thus  Helman 
and  Kalning  prepared  a  substance  designated  mallein.  winch  has 
been  the  subject  of  numerous  investigations,  especially  by  Preuss 
Pearson,  Foth,  Babes,  Nocard,  and  Bonome. 

Inoculation  of  mallein  into  animals  suffering  from  glanders  pro- 
duces at  the  injected  point  a  hot,  painful  tumefaction  which  incr<  s  - 
for  twenty-four  or  thirty-six  hours,  and  disappears  in  eight  or  ten 
days.  Synchronously  the  general  state  is  modified.  There  is  pros- 
tration; the  animal  looks  depressed,  anxious:  its  breathing  is  ac- 
celerated, and  it  may  have  chills  and  convulsions.  A  febrile  move- 
ment finally  sets  in  which  reaches  its  maximum  after  ten  or  twelve 

40 


626  INFECTIOUS  DISEASES. 

hours,  seldom  later.  The  rise  in  temperature  amounts  to  2.7°  to 
4.5°  F.  (1.5°  to  2.5°  C).  It  is  to  be  noted  that  the  mallein  test  is 
conclusive  only  in  those  cases  in  which  the  inoculation  is  made  upon 
animals  having  previously  been  at  rest  for  forty-eight  hours  and 
protected,  after  inoculation,  against  atmospheric  variations. 

If  reaction  is  clear — i.  e.,  if  the  thermal  elevation  is  regularly 
produced  and  reaches  2.7°  F.  (1.5°  C),  the  existence  of  glanders 
may  be  affirmed  with  a  fair  degree  of  assurance.  If  the  temperature 
is  raised  3.6°  F.  (2°  C),  diagnosis  is  positive,  and  the  animal  is  killed. 
When  reaction  is  incomplete  or  irregular  the  animal  is  left  at  rest 
for  four  to  six  weeks,  and  then  the  experiment  is  resumed  with 
little  larger  doses. 

The  employment  of  mallein  has  rendered  immense  service.  By 
revealing  with  a  fair  degree  of  certainty  the  existence  of  glanders 
and  treat  it  from  the  very  beginning,  mallein  will  certainly  serve 
to  decrease  and  finally  extinguish  this  disease.  The  mallein  test 
may  also  be  applied  to  man,  provided  small  doses  are  employed. 
It  has  thus  been  injected  with  success  by  Bonome  and  by  Buscke. 

Recapitulation.  The  foregoing  various  scientific  procedures  of 
diagnosis,  which  are  mostly  drawn  from  recent  bacteriological  dis- 
coveries, may  render  immense  service  to  the  nosologist  by  enabling 
him  to  give  a  solid  basis  to  clinical  observations;  but  they  are  of 
less  importance  in  practice.  In  spite  of  their  apparent  simplicity, 
they  require  a  vast  amount  of  technical  experience,  and  the  positive 
character  of  laboratory  researches  renders  possible  quite  harmful 
errors.  It  should  not,  therefore,  be  imagined,  as  is  too  often  done, 
that  bacteriology  will  furnish  the  physician  with  simple  and  certain 
procedures.  The  difficulties,  although  of  a  different  character,  exist 
none  the  less.  Even  supposing  that  the  practitioner  has  acquired 
sufficient  skill  to  utilize  the  modern  methods  of  investigation,  it 
must  be  remembered  that  bacteriology  is  incapable  of  solving  all 
the  problems  which  confront  the  physician  in  connection  with  each 
particular  case  observed.  When  he  recognizes  that  the  disturbances 
are  due  to  a  definite  microbe  he  will  not  have  finished  his  task.  A 
complete  diagnosis  must  answer  many  other  questions.  For  ex- 
ample, a  patient  whose  expectorations  contain  the  pneumococcus, 
and  whose  respiratory  apparatus  is  the  seat  of  a  lesion  dependent 
upon  this  microbe,  may  have  a  bronchitis,  or  a  capillary  bronchitis, 
or  a  bronchopneumonia,  or  a  fibrinous  pneumonia.  The  same 
microbe  is  concerned  in  all  four  instances;  but  the  affection  pro- 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES.    627 

duced  is  quite  different  from  the  quadruple  Btandpoinl  of  anatomico- 
pathological  localization,  evolution,  prognosi  .  and  treatment.  I' 
may  be  answered  bhal  the  nature  of  the  morbid  reaction  i  no1  of 
prime  importance,  and  thai  the  point  to  be  decided  i-  the  nature 
of  the  pathogenic  agent.  As  soon  ac  this  is  done  the  specific  treat- 
ment can  be  applied  and  the  evolution  of  the  disease  arrested.  For 
the  present,  however,  this  is  a  dangerous  Utopia.  Even  in  thi 
of  diphtheria,  the  only  infection  for  which  we  pot  i  iecific,  the 

physician  will  be  bitterly  disappointed  if  he  fancies  thai  i1  suffices 
to  inject  antitoxin  as  soon  ;is  the  bacillus  is  discovered.  On  the 
contrary,  lie  must  establish  a  complete  diagnosis,  determine  the 
state  and  extent  of  the  lesions,  and  learn  under  what  conditions 
these  develop  and  in  what  kind  of  soil  they  evolve. 

Rules  of  Clinical  Diagnosis.  It  is  evident  that  the  questions 
which  must  be  solved  in  the  presence  of  a  patient  apparently  suffer- 
ing from  an  infection  vary  from  one  case  to  another.  They  may, 
nevertheless,  be  grouped  in  the  following  manner: 

1.  What  are  the  present  disturbances?  The  sensations  felt  by 
the  patient,  the  objective  phenomena  which  he  presents  enable  the 
physician  to  answer  this  first  question.  He  may  thus  lay  down 
the  symptoms  which  he  observes. 

2.  What  is  the  immediate  cause  of  these  disturbances,  namely, 
with  what  organs  or  systems  are  they  to  be  associated?  This  second 
question  is  more  difficult.  In  fact,  symptoms  are  divided  into  two 
groups.  Some  of  them  express  the  suffering  of  an  organ  and  imme- 
diately draw  the  attention  of  the  physician  to  this  organ.  Cough 
or  dyspnea  leads  him  to  auscultate  the  lungs.  Palpitation  of  the 
heart  leads  him  to  examine  the  heart,  and  impotence  of  the  lower 
extremities  leads  him  to  study  the  nervous  system.  If.  however, 
he  weighs  the  close  synergies  connecting  the  various  parts  of  the 
organism  he  will  remember  that  the  disorders  of  these  organs  may 
depend  upon  some  other  organ.   Thus  we  arrive  at  the  third  question. 

3.  Are  the  suffering  parts  primarily  or  secondarily  affected'?  Are 
their  disorders  or  lesions  independent  or  due  to  the  same  cause? 
Among  the  organs  affected,  in  which  one  did  the  disorders  upon 
which  the  other  symptoms  depend  first  become  manifest'? 

All  these  questions  may  be  solved  only  in  one  way.  The  physician 
must  examine  systematically  the  various  parts  of  the  organism, 
those  which  seem  to  be  diseased  as  well  as  those  which  appear 
healthy. 


628  INFECTIOUS  DISEASES. 

4.  The  succession  of  the  present  symptoms  having  been  estab- 
lished, the  physician  must  solve  the  question  whether  the  present 
affection  is  the  result  of  a  previous  disease  or  whether  it  is  a  primary 
malady. 

5.  In  the  latter  instance  he  must  investigate  the  nature  of  this 
disease  and  its  place  in  nosology.  It  is  here,  and  here  only,  that 
modern  procedures  intervene,  and  bacteriology,  at  least  in  certain 
cases,  may  profitably  be  resorted  to.  However,  even  when  a  search 
for  the  microbe  enables  the  physician  to  assign  to  the  disease  its 
true  place  in  nosology,  his  task  is  not  yet  completed.  He  has  a  last 
and,  perhaps,  the  most  important  question  to  solve,  for  the  diagnosis 
and  part  of  the  treatment  depend  upon  it,  namely: 

6.  In  what  soil  is  the  disease  evolving?  What  clinical  form  does 
it  assume?  What  organs  are  secondarily  involved?  Having  made 
a  complete  examination  of  the  patient,  the  physician,  in  most  cases, 
finds  sufficient  data  to  answer  the  questions  connected  with  the 
diagnosis.  Although  he  cannot  always  reach  definite  conclusions, 
he  can  at  least  make  a  more  or  less  close  approach  to  accuracy. 
At  the  beginning  of  the  disease  he  may  remain  in  doubt,  but  he 
hesitates  only  between  two  or  three  hypotheses,  and,  in  general, 
after  a  daj^  or  two  the  evolution  of  the  disease,  by  modifying  the 
clinical  aspect,  leads  him  to  an  exact  and  definitive  conception  of 
the  events.  Thus,  for  example,  he  is  called  to  decide  the  case  of 
a  child  or  a  young  man  suddenly  attacked  by  angina.  He  finds 
fever,  a  rapid  pulse,  a  coated  tongue,  and  a  red  throat  with  some 
yellowish  exudate  upon  the  tonsils.  The  diagnosis  of  acute  angina 
is  evident,  but  what  is  the  nature  of  this  angina?  This  is  more 
difficult  to  determine,  and  yet  the  question  is  of  prime  importance 
from  a  prognostic  and  therapeutic  standpoint.  The  sudden  onset, 
the  pultaceous  aspect  of  the  tonsillar  deposit,  and  the  frankly 
inflammatory  reaction  lead  the  physician  to  eliminate  diphtheria. 
But  is  the  case  one  of  simple  angina  or  of  a  scarlatinal  angina? 
The  age  of  the  subject,  intensity  of  the  fever,  the  intense  redness 
of  the  throat,  the  rapidity  of  the  pulse,  and  at  times  the  existence 
of  a  concomitant  epidemic,  cause  the  physician  to  incline  to  a 
diagnosis  of  scarlatina.  A  final  decision  is  impossible,  however. 
He  must  wait  for  the  appearance  of  the  eruption,  that  is,  until  the 
third  day  of  the  disease,  in  order  to  definitely  decide  the  question. 
In  this  instance,  a  symptomatic  manifestation  of  prime  importance 
in  diagnosis  is  lacking. 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES.    629 

Id  other  cases  an  exaci  diagnosis,  which  3eero    to  be  justified  l>y 
no  symptom,  may  be  laid  down  from  the  very  beginning.    Thus  ;i 
child  eight  or  ten  years  of  age  is  suddenly  taken  by  intei 
It  suffers  from  dyspnea  and  a  very  irritating  dry  cough.    The  face 
is  congested,  the  cheeks  red,  and  the  temperature  a1  lor  I      K)  I 
Although  auscultation  gives  negative  results,  the  physician  diagi 
pneumonia,  and,  in  reality,  after  twenty-four  hours,  sometimes  after 
two  or  three  rhiys,  the  characteristic  bronchial  murmur  i-  heard. 
Owing  to  a  little  practice  the  diagnosis  was  made  a1    the  outsel   i/i 
spite  of  the  absence  of  stethoscopic  signs  and  in  spite  of  the  presence, 
in  certain  instances,  of  nervous  phenomena  and  even  convulsions, 
which  might  first  lead  to  a  diagnosis  of  meningitis. 

It  would  be  easy  to  multiply  illustrations.  These  few  suffice  to 
establish  that,  in  most  infections,  diagnosis  may  be  made  if  the 
whole  organism  is  systematically  and  minutely  examined. 

When  the  physician  has  recognized  the  nature  of  the  disease  he 
has  not  yet  completed  his  task.  Let  us  suppose  the  case  of  a  man 
who  has  been  suddenly  taken  by  a  chill,  followed  by  pain  in  the  side. 
an  irritating  cough,  brick-dust  expectoration,  and  intense  fever. 
On  auscultation  we  find  in  one  of  the  lungs  a  focus  of  crepitant 
rales  or  tubal  murmur.  The  state  of  the  lung  explains  all  the  dis- 
orders, and  the  evolution  of  the  disease  enables  us  to  state  that  we 
are  dealing  with  an  infection — i.  e.,  pneumonia.  We  have  thus 
answered  all  the  questions  which  we  had  to  solve,  except  the  last 
one.  It  was  easy  to  make  the  diagnosis  of  pneumonia  in  this 
instance. 

It  is  more  difficult  to  determine  in  what  soil  the  infection  evolves. 
In  this  connection  it  is  important  carefully  to  interrogate  the  patient 
as  regards  his  hereditary  as  well  as  personal  morbid  antecedents. 
In  this  connection,  also,  all  the  viscera  must  be  carefully  examined. 
The  physician  does  well  to  auscultate  the  lungs  in  order  to  recognize 
the  disease;  but  he  must  never  be  contented  with  so  summary  a 
diagnosis.  The  prognosis  and  the  treatment  are  to  be  based  upon 
the  knowledge  he  acquires  of  the  previous  condition  of  the  subject 
and  the  present  state  of  the  various  organs.  Then,  and  then  only. 
will  he  reach  a  complete  diagnosis  and  be  able  to  foretell  the  evolution 
of  the  disease.  If  pneumonia  develops  in  a  young  and  vigorous 
individual,  recovery  is  the  rule.  If  it  occurs  in  an  aged  person, 
the  termination  is  in  most  cases  fatal.  In  both  of  these  instances 
pathology   seems  to   furnish   sufficient   information.      Let  us  now 


630  INFECTIO  US  DISEASES. 

consider  an  apparently  vigorous  patient  attacked  by  pneumonia. 
One  might  believe  that  he  will  recover  without  much  hinderance.  ( )n 
making  a  systematic  examination  of  his  organs  and  an  analysis  of 
the  urine  a  lesion  until  then  latent  is  discovered,  a  cardiac  affection, 
a  sclerosis,  or  else  albuminuria,  or  glycosuria,  or,  lastly,  there  are 
found  secondary  localizations  in  other  organs,  endocarditis  or  myo- 
carditis. The  evolution  will  then  be  different.  An  exact  conception 
of  the  disease  is  obtained  by  careful  examination  of  the  entire 
organism. 

The  example  which  we  have  chosen  was  a  simple  one.  At  any 
rate,  it  may  be  said  that  it  is  relatively  easy  to  diagnose  an  infectious 
disease.  The  physician  has  to  deal  with  a  recent  acute  evolution, 
all  the  phases  of  wThich  are  observable,  since  he  is  examining  the  case 
at  a  stage  quite  near  the  beginning  of  the  evolution.  In  most  cases, 
in  order  to  arrive  at  a  diagnosis,  it  suffices  to  have  studied  pathology 
well.  The  only  important  point  is  to  make  a  complete  diagnosis, 
for,  as  we  have  often  repeated,  the  manifestations  are  far  more 
diffuse  than  is  at  first  believed.  The  microbic  toxins  affect  the 
whole  economy,  and  the  duty  of  the  clinician  is  to  learn  what  parts 
are  affected  and  in  what  degree  they  are  involved.  To  find  the 
designation  under  which  the  infection  is  to  be  classed  is  a  relatively 
easy  task:  but  diagnosis,  however  exact  it  may  appear  to  be,  is 
incomplete  and  insufficient,  and  answers  only  the  first,  the  easiest 
and  the  least  important  part  of  the  problem. 

In  order  to  facilitate  the  task  of  the  physician,  nosologists  have 
admitted  a  certain  number  of  clinical  forms  in  infectious  diseases. 
Taking  typhoid  fever  and  pneumonia  as  examples,  we  have  shown 
how  it  is  possible,  by  considering  either  the  state  of  the  subject  or 
the  general  disturbances  or  the  localizations,  to  classify  the  various 
types  and  furnish  precise  indications  for  the  guidance  of  the  physician. 
These  forms,  however  numerous  they  may  be,  do  not,  of  course, 
respond  to  all  the  clinical  varieties  and  their  innumerable  variations ; 
but  they  may  supply  valuable  data,  and  must,  therefore,  be  most 
carefully  studied.  In  certain  instances  the  complexity  of  the 
clinical  form  is  due  to  the  coexistence  of  various  manifestations  or 
multiple  localizations.  It  is,  therefore,  very  difficult  at  times  to 
connect  them  with  each  other.  Thus,  we  may  have  to  deal  with  a 
case  of  erysipelas  in  which,  at  a  given  moment,  a  pulmonary  murmur 
is  detected.  Is  the  process  a  streptococcic  infection — i.  e.,  a  visceral 
localization  dependent  upon  the  agent  which  has  caused  the  first 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES.    <;;',] 

disease?  or  is  it  an  infection  due  to  a  superadded  microbe,  the 

I >i kmi 1 1 k >f< if-ci is ?    lioi.li  varieties  of  pneumonia  have  been  ob  ei 
in  erysipelas,  and,  withoul  bacteriological  examination  of  the  sputa, 
it  is  generally  impossible  to  make  the  diagno  i 

The  difficulty  is  still  greater  when  the  pathogenic  agenti  are 
unknown.  In  an  individual  presenting  a  scarlatiniform  eruption 
coincident  with  other  infectious  manifestations,  how  can  we  affirm 
whether  the  case  is  one  of  erythema  or  a  true  scarlatina?  It  would 
be  equally  right  to  hesitate  in  certain  cases  in  which  multiple  artic- 
ular symptoms  occur  in  scarlatinal  patients  a1  the  period  of  con- 
valescence. Do  they  depend  upon  scarlatina  or  a  concomitanl 
acute  articular  rheumatism?  Nol  infrequently  the  physician  re- 
mains in  doubt  with  regard  to  all  these  questions.  In  order  to 
classify  and  interpret  the  disturbances,  the  physician  does  not  need, 
as  is  often  stated,  a  particular  talent,  a  sort  of  divining  gift.  The 
skill  of  making  a  diagnosis  is  not  inborn.  On  the  contrary,  it  is 
acquired  by  theoretical  and  pr.-iclical  study  of  pathology  and  by 
repeated  examination  of  patients.  As  a  matter  of  fact,  we  see  in 
clinics  cases  far  more  complex  than  the  study  of  pathology  makes 
us  believe.  Didactic  studies  give  only  schematic  descriptions. 
They  consider  diseases  in  their  fundamental  and  constant  characters, 
regardless  of  the  soil  in  which  they  run  their  course.  It  is  precisely 
because  this  soil  is  so  eminently  variable  that  clinical  types  are  so 
numerous  and  varied.  The  duty  of  the  physician  is,  therefore,  to 
determine  the  soil  in  which  the  disease  evolves,  and  from  this  deter- 
mination he  must  draw  the  greater  part  of  his  knowledge  of  its 
ulterior  evolution. 

After  the  physician  has  succeeded  in  discovering  the  present  state 
of  the  patient,  his  resistance,  his  reactionary  aptitudes,  the  functional 
activity  and  alterations  of  his  organs,  he  will  be  in  a  position  to 
predict  the  evolution  of  the  process  he  observes.  To  answer  this 
last  question  is  to  establish  a  prognosis,  that  is,  to  solve  the  most 
difficult  and  important  problem  in  medical  art. 

Prognosis. 

It  is  evident  that,  in  the  matter  of  prognosis,  the  nature  of  the 
disease  is  first  to  be  considered.  Certain  infections  almost  always 
terminate  fatally,  and  others  end  in  recovery.  In  such  cases  prog- 
nosis is  drawn  simply  from  diagnosis.     Tubercular  meningitis,  acute 


632  ISFECTIOUS  DISEASES. 

mania,  and  hydrophobia  are  always  or  nearly  always  fatal.  On  the 
other  hand,  varicella,  mumps, herpetic  anginas, and  simple  pneumonia 
in  children  always  or  nearly  always  end  in  recovery.  Nothing  seems 
to  be  simpler.  Even  in  these  cases,  however,  there  are  exceptions. 
Varicella  at  times  proves  fatal,  and  a  good  number  of  distinguished 
physicians  assort  that  tubercular  meningitis  is  curable.  These  ex- 
ceptions, one  may  say,  should  not  be  taken  into  account.  Let  us, 
therefore,  set  aside  these  facts  and  consider  the  most  frequent  cases. 
When  we  have  to  deal  with  an  infection  with  variable  prognosis, 
whence  shall  we  draw  our  data  of  appreciation?  We  may  first 
resort  to  statistics.  From  this  point  of  view  I  have  looked  up  the 
observations  in  our  wards  during  the  last  five  years.  These  obser- 
vations are  8832  in  number,  comprising  602  fatal  cases,  that  is,  a 
proportion  of  6.8  per  cent.  From  tabulation  of  these  figures  v?e 
may  draw  certain  important  conclusions  with  reference  to  prog- 
nosis. In  fact,  it  will  not  suffice  to  consider  the  results  in  a  general 
way.  Although  it  is  interesting  to  know  what  the  general  mor- 
tality is  in  each  disease,  it  is  indispensable  to  push  analysis  a  little 
further.  Here  are  some  conclusions  regarding  the  influence  of  age 
and  sex  upon  prognosis : 

Influence  of  Age.  It  may  broadly  be  stated  that  mortality  is 
very  high  during  infancy  and  is  considerably  reduced  after  two 
years  of  age.  In  the  adult,  according  to  the  disease  under  considera- 
tion, mortality  may  be  greater  or  less  than  that  in  second  childhood. 
Thus,  in  measles,  scarlatina,  varicella,  diphtheria,  and  anginas  the 
mortality  in  adults  is  far  belowr  that  in  children.  Such  is  not  the 
case  with  erysipelas.  The  mortality,  which  is  45  per  cent,  before 
two  j^ears,  falls  to  0  between  twro  and  fourteen  years  of  age.  Between 
fifteen  and  thirty  years  it  hardly  exceeds  1  per  cent.;  then  it  rises 
with  age.  It  oscillates  around  4  or  5  per  cent,  from  thirty-one  to 
fifty  years  of  age.  It  may  be  remarked  that,  during  infancy,  ery- 
sipelas kills  of  itself  by  streptococcic  generalization.  In  the  adult, 
on  the  contrary,  death  commonly  results  from  a  complication  or  a 
previous  organic  lesion  which  has  weakened  the  resistance.  The 
influence  of  age  is  no  less  important  in  other  diseases,  especially  in 
measles.  During  infancy  the  mortality  reaches  27.7  per  cent  It 
falls  to  6.6  per  cent,  in  childhood,  and  to  0.8  per  cent,  in  adults. 
Three  principal  factors  explain  the  higher  percentage  in  young 
children,  namely,  bronchopneumonia,  tuberculosis,  and  suppura- 
tions and  gangrenes.     The  influence  of  measles  upon  the  course  of 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISE  ISEl 

tuberculosis  has  long  been  noted.    The  younger  the    ubjed   the 
more  marked  is  the  action  of  this  eruptive  fever  upon  the  evolution 
of  tuberculosis.     Bronchopneumonia,  suppurations,  and  gang] 
(Icpciid  upon  common  germs,  which  are  closely  allied  to  each  other, 
and  upon  pus-cocci.     Young  children  are  particularly  predisp 
to  the  action  of  these  bacteria,  but  they  run  the  risk  of  infection 
especially  when   they  are  placed  under  bad  hygienic  conditions. 
The  frequency  and  gravity  of  superadded  pyogenic  Infections  in 
young  children  are  likewise  proved  by  the  study  of  other  disc 
Scarlatina,  which  has  little  tendency  to  afifecl  the  respiratory  <<<■_ 
may  kill  al   this  age  by  bronchopneumonia.      Finally,  varicella, 
which  is  too  often  considered  as  a  mild  disease,  gives  a  mortality 
of  more  than  7  per  cenl . 

Influence  of  Sex.  The  influence  of  sex,  which  is  nil  during  child- 
hood, varies  in  adult  age  according  to  the  disease  under  considera- 
tion. According  to  our  statistics,  mortality  is  the  same  in  hoth 
sexes  for  scarlatina,  somewhat  higher  in  men  in  measles  and  especi- 
ally in  variola.  For  the  latter  infection,  the  mortality  is  26.2  per 
cent,  in  men,  and  22.1  per  cent  in  women.  The  differences  are 
analogous  in  erysipelas.  In  this  affect  ion  the  mortality  is  5.99  per 
cent,  in  men,  and  3.67  per  cent,  in  women.  I  believe  that  the 
higher  percentage  of  mortality  in  males  is  due  to  the  influence  of 
alcohol.  Chronic  intoxication  by  alcohol  causes  nutritional  disturb- 
ances and  visceral  lesions  which  lend  a  particularly  serious  character 
to  infections.  In  measles  and  scarlatina  mortality  is  nearly  the 
same  in  both  sexes,  because  the  individuals  attacked  are  still  very 
young  and  are  not  yet  sufficiently  impregnated  with  alcohol.  Variola 
and  erysipelas  are  often  observed  in  individuals  more  advanced  in 
age,  and,  therefore,  the  mortality  in  men  is  higher  than  in  women. 

This  is  the  information  that  may  be  drawn  from  the  statistics. 
In  spite  of  their  interest  they  are  insufficient  to  assist  materially 
in  diagnosis.  Therefore,  in  order  to  foretell  the  probable  evolution 
of  a  disease  it  is  necessary  to  consider  the  data  of  another  order. 

Influence  of  Epidemics.  The  elements  which  serve  as  a  basis 
for  prognosis  may  be  divided  into  two  groups.  On  the  one  hand, 
the  characters  of  the  disease  must  be  considered,  viz..  the  condition? 
under  which  it  is  developed,  the  symptoms  it  presents,  and  the  course 
it  follows.  Next,  the  soil  in  which  the  disease  evolves  is  to  be 
studied.  The  first  information  is  furnished  by  epidemiology.  It  is 
known  that   at   certain  moments  diseases  become   aggravated  or 


034  INFECTIOUS  DISEASES. 

attenuated.  We  often  notice  changes  in  the  evolution  of  influenza, 
pneumonia,  and  typhoid  fever.  For  a  few  years  past  diphtheria 
was  very  benign.  At  present  it  seems  to  assume  a  more  serious 
character.  The  same  remark  may  be  made  with  regard  to  scar- 
latina. Moreover,  it  is  known  that  in  the  course  of  the  same  epi- 
demic the  gravity  follows  a  course  nearly  parallel  to  that  of  mor- 
bidity. Benign  cases  are  frequent  at  the  end  of  the  epidemic. 
The  hygienic  conditions  under  which  a  patient  is  placed  should  also 
be  taken  into  consideration,  whether  he  is  being  treated  in  a  hospital 
or  at  home.  These  are  evident  truths  upon  which  it  is  useless  to 
dwell. 

Importance  of  Etiological  Conditions.  Certain  importance  is 
often  attached  to  the  knowledge  of  the  etiological  conditions.  It 
has  been  demonstrated,  however,  by  a  great  many  examples  that  a 
disease  contracted  from  a  profoundly  infected  individual  may  prove 
to  be  benign,  and  vice  verm.  In  this  connection,  nothing  is  more 
instructive  than  the  study  of  venereal  infections.  In  many  cases 
in  which  these  affections  have  been  transmitted  to  several  individuals 
under  etiological  conditions  as  similar  as  possible,  the  evolution  in 
the  various  subjects  has  been  quite  different.  In  certain  cases, 
however,  an  exalted  virus  produces,  by  contagion,  grave  diseases. 
To  be  convinced  of  this,  it  will  suffice  to  state  what  occurs  with 
regard  to  pneumonia  in  certain  family  epidemics.  By  thus  follow- 
ing the  course  of  these  infections  successively  contracted  we  may 
often  see  the  process  become  more  and  more  serious  as  it  spreads. 
The  person  first  attacked  has  a  benign  infection,  which  assumes  a 
progressively  graver  character  as  it  is  transmitted  to  persons  about 
him.  Analogous  observations  have  been  made  by  Dr.  Quelme  with 
regard  to  dysentery  in  Bretagne. 

In  the  case  of  an  inoculated  infection  prognosis  depends  partly 
upon  the  mode  of  entrance  of  the  virus.  The  gravity  of  extragenital 
syphilis  has  long  been  known.  A  better  example  is  furnished  by 
hydrophobia.  Not  to  speak  of  cases  in  which  bites  inflicted  upon 
parts  protected  by  clothing  produce  no  symptoms,  statistics  show 
that  wounds  of  the  fingers  and  face  are  particularly  serious,  because 
these  regions  are  rich  in  nervous  terminations.  The  mortality  is 
about  87  per  cent,  for  bites  of  the  face,  66  per  cent,  for  those  of  the 
hands,  29  per  cent,  for  those  of  the  upper  extremities,  and  19  per 
cent,  only  for  those  of  the  lower.  Finally,  it  may  be  stated  that 
in  the  case  of  infections  which  may  be  transmitted  by  several  pro- 


DIAGNOSIS  and  PROGNOSIS  OF  INFECTIOUS  DISEASES.    636 

cedures  prognosis  is  least  serious  in  accidental  inoculation.  Glanders 
produced  by  subcutaneous  inoculation  is  quite  often  cured.  I'  if 
likewise  known  that  the  prognosis  of  anatomical  tubercle  i.e.,  con- 
tracted at  necropsy    is  generally  favorable. 

Importance  of  the  Duration  of  Incubation  and  of  the  Mode  of 
Invasion.  When  the  momenl  in  which  the  infection  has  occurred 
can  be  determined,  it  is  possible  lo  <lr;i,w  some  information  from  the 
length  of  incubation.  We  have  already  Qoticed  thai  the  period  of 
incubation  is  abridged  under  two  quite  dif'ferenl  circums1;inccs, 
namely,  when  the  virus  is  very  active  and,  consequently,  the  prog- 
nosis is  evidently  grave,  or  when  the  organism  is  capable  of  very 
energetic  reaction  and  the  incubation  is  short  and  of  f;ivor;ible  signifi- 
cance. The  difference  will  be  appreciated  in  view  of  the  concomitanl 
circumstances. 

The  same  remarks  are  applicable  to  the  mode  of  invasion.  With 
a  very  sudden  and  tumultuous  onset,  an  infection  may  be  very 
benign  and  even  very  short.  Therefore,  to  exactly  appreciate  the 
importance  of  the  mode  of  onset,  we  must  consider  the  accompanying 
phenomena.  If  these  are  not  very  intense  this  suddenness  of  the 
initial  manifestations  indicates  a  favorable  evolution.  If  they  are 
intense,  a  grave,  or  at  least  a  serious,  form  may  be  predicted.  In 
certain  instances  the  knowledge  of  the  initial  manifestations  may 
serve  in  diagnosis.  Thus,  surgeons  have  established  an  important 
difference  between  phlegmons  which  begin  with  local  phenomena  and 
those  attended  from  the  first  by  general  reactions.  In  the  latter 
instance  the  profounder  impregnation  of  the  organism  is  connected 
with  a  greater  gravity  of  the  process. 

A  relationship  is  generally  believed  to  exist  between  the  duration 
of  invasion  and  the  gravity  of  a  disease.  This  the  author  does  not 
believe  to  be  true  except  with  respect  to  variola.  In  this  infection 
a  short  invasion,  not  exceeding  two  days  or  two  and  a  half  days,  is 
a  sign  of  confluent  variola.  An  invasion  lasting  three  or  four  days 
indicates  a  discrete  variola.  It  is  true  that  an  eruption  beginning 
after  four  full  days  is  seldom  confluent.  This,  however,  is  acceptable 
with  some  reservation. 

Bases  of  Prognosis  at  the  Stationary  Period.  As  a  rule,  when  a 
disease  has  reached  the  stationary  period  the  physician  possesses  all 
the  necessary  elements  for  prognosis.  These  elements  are  four  in 
number:  First,  the  local  lesion  or  the  principal  expression  of  the 
infection — the  eruption  in  cases  of  eruptive  fevers.     Second,  the 


636  INFECTIOUS  DISEASES. 

state  of  the  parts  surrounding  the  local  lesion.  Third,  the  general 
phenomena.     Fourth,  the  condition  of  the  principal  organs. 

Let  us  immediately  remark  that  if  an  analytical  examination  is 
necessary,  the  prognosis  must  be  established  in  view  of  the  ensemble 
of  the  researches  above  indicated.  To  determine  the  extent  of  the 
local  lesion  or  the  intensity  of  the  general  phenomena  does  not  suffice- 
These  two  orders  of  manifestations  must  be  compared  in  order  to 
draw  a  conclusion  It  may  broadly  be  stated  that  prognosis  is  grave 
in  proportion  as  the  local  lesion  is  intense  and  especially  extensive. 
This  is  true  as  regards  pneumonia  as  well  as  eiysipelas  and  the  erup- 
tive fevers,  and  particularly  so  with  respect  to  variola.  The  prog- 
nosis of  the  latter  disease  depends  entirely  upon  the  character  of  the 
eruption.  Of  course,  the  study  of  the  general  phenomena  is  impor- 
tant, but  that  of  the  cutaneous  manifestations  is  still  more  important. 
The  condition  of  the  parts  surrounding  the  local  lesion  must,  as  a 
rule,  be  taken  into  consideration.  In  the  case  of  pneumonia  and 
tuberculosis  the  information  furnished  by  the  examination  of  the 
portions  of  parenchyma  spared  by  the  principal  process  is  of  consid- 
erable importance.  The  phenomena  of  congestion  or  edema  which 
may  take  place  therein  greatly  affect  the  prognosis. 

As  already  stated  the  conditions  of  the  local  lesion  and  of  the 
general  state  must  be  compared.  Violent  general  reactions  are  much 
less  grave  than  adynamic  manifestations. 

Finally,  the  examination  must  be  completed  by  determining  the 
condition  of  the  organs,  heart,  lungs,  and  liver,  and  by  analyzing  the 
urine.  Thus  information  is  obtained  concerning  the  function  of  and 
the  possible  complications  occurring  in  the  viscera.  This  comple- 
mentary examination  shows  the  influence  of  the  present  infection 
upon  the  principal  organs,  and  thus  enables  us  to  form  an  idea  of  the 
previous  condition  and  pre-existing  lesions  of  the  organs.  In  this 
manner  we  obtain  valuable  indications  for  prognosis,  for  it  is  not 
sufficient  to  determine  the  characters  of  the  present  disease,  its 
intensity,  and  the  lesions  which  it  produces  or  complications  to  which 
it  gives  rise.  We  must  know  the  soil  in  which  the  disease  evolves 
in  order  to  establish  the  prognosis. 

We  hardly  need  dwell  upon  the  importance  of  the  general  state  of 
the  individual  at  the  time  when  he  is  attacked  by  an  intercurrent 
disease.  We  know  the  gravity  of  an  infection  attacking  a  cachectic, 
emaciated  individual  having  suffered  privations,  exposure,  overwork, 
and  excessive  fatigue.     In  all  debilitated  individuals  evolution  is 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES.     637 

grave,  and,  the  defensive  reactions  being  often  nearly  impossible,  •'' 
fatal  termination  soon  takes  place.  Fatigue  and  overwork  not  only 
render  prognosis  unfavorable  by  aggravating  the  cour  e  of  the  dis- 
ease, but  also  by  favoring  certain  morbid  localization  .  We 
already  referred  to  the  frequency  of  myocarditii  in  overworked  indi- 
viduals. In  certain  cases  the  cardiac  infection  ends  in  the  formation 
of  an  abscess.  In  other  instances  overexertion  gives  rise  to  cerebral 
localizations.  It  will  suffice  to  recall  the  frequency  of  delirium  under 
these  conditions.  We  have  a  more  palpable  illustration  in  cerebral 
rheumatism,  a  grave  manifestation  which  is  observed  only  among  a 
certain  class  of  individuals. 

Nutritional  disturbances  dependent  upon  a  diathetic  state  like 
exercise  an  unfavorable  influence  upon  the  course  of  infections.  The 
gravity  of  infections  in  the  obese  may  be  cited  as  an  example  of  this. 
The  very  thick  adipose  tissue  seems  to  prevent  the  dissipation  of  heat 
in  fever.  On  the  other  hand,  the  disorders  of  nutrition  engendered 
by  obesity  render  the  reactions  sluggish  and  less  energetic.  Hence. 
after  the  termination  of  the  disease  its  effects  are  prolonged  beyond 
the  usual  limits.  The  ill-nourished  skin  is  easily  invaded  by  external 
germs.  Not  infrequently  furuncles,  anthrax,  and  especially  sloughs 
occur,  particularly  in  the  sacral  region. 

Among  the  diseases  connected  with  disturbances  of  nutrition  we 
may  cite  gout  and  diabetes.  In  this  connection  gout  is  of  little 
importance.  We  have  observed  several  cases  of  erysipelas  in  gouty 
individuals  in  whom  the  evolution  terminated  in  a  favorable  manner. 
The  role  of  diabetes  is  more  important.  It  is  known  that  this  di- 
predisposes  to  cutaneous  infections,  pulmonary  inflammations  and 
tuberculosis.  It  imparts  to  these  processes  a  particularly  rapid  and 
grave  evolution.  Infections  of  the  skin  and  lungs  are  easily  compli- 
cated with  gangrene.  In  other  cases  pneumonia  assumes  a  galloping 
course.  The  gravity  of  infections  should  not,  however,  be  exagger- 
ated as  regards  diabetic  patients.  We  have  seen  several  such  patients 
attacked  by  erysipelas,  and  all  recovered.  It  is  true  that  the  infec- 
tion was  particularly  intense,  attended  by  delirium,  and  prolonged 
beyond  the  average  duration. 

Another  element  of  prognosis  is  drawn  from  the  knowledge  of  pre- 
vious infections  and  especially  intoxications  of  the  individual.  With 
reference  to  relapsing  infections  it  has  been  asserted  that  successive 
attacks  gradually  lose  their  intensity.  This  law  does  not  seem  to 
the  author  quite  true.    It  is  not  true  with  regard  to  erysipelas,  and 


638  IXFECTIO  US  DISEASES. 

many  case?  are  on  record  in  which  individuals  have  succumbed  to  a 
second  or  third  attack  of  variola. 

In  treating  of  microbic  associations  we  have  shown  the  role  of 
previous  or  concomitant  infections  and  emphasized  the  fact  that 
results  varied  according  to  the  case  under  observation.  It  may  be 
recalled  that  erysipelas  occurring  during  convalescence  from  scarla- 
tina is  very  benign,  while  pneumonia  supervening  in  the  course  of 
erysipelas  is  always  highly  dangerous.  It  is  evident  that  a  pre- 
existing chronic  infection  aggravates  the  prognosis  of  an  intercurrent 
infection.  This  is  true  as  regards  syphilis,  malaria,  and  especially 
tuberculosis.  Furthermore,  intercurrent  disease  may  awaken  a  pre- 
vious infection,  bring  about  a  recurrence  of  malarial  paroxysms,  and 
impart  to  a  chronic  tuberculosis  an  acute  course. 

Previous  intoxications  likewise  modify  prognosis.  Owing  to  dis- 
turbances of  nutrition  and  the  organic  lesions  to  which  they  give 
rise,  they  aggravate  infections.  Alcoholism  is  to  be  considered  in  a 
particular  manner  in  this  connection.  It  is  not  so  much  by  ques- 
tioning the  patient  as  by  analysis  of  the  phenomena  observed,  and 
particularly  cerebral  symptoms,  that  the  physician  recognizes  this 
intoxication.  We  may  repeat,  however,  that  alcohol  acts  not  only 
upon  the  nervous  system,  but  causes  important  lesions  in  the  viscera 
and  particularly  in  the  liver.  We  are  thus  led  to  investigate  the  role 
of  visceral  affections  upon  the  course  of  infections  and  their  impor- 
tance from  a  prognostic  standpoint. 

Role  of  Previous  Visceropathies.  As  has  already  been  stated,  the 
lesions  of  the  heart  do  not  markedly  aggravate  the  prognosis.  Con- 
trary to  what  might  be  supposed,  a  chronic  endocarditis  seldom  forms 
the  focus  for  a  new  cardiac  localization.  The  prognosis  depends,  not 
upon  the  extent  or  the  nature  of  the  valvular  lesion,  but  upon  the 
condition  of  the  cardiac  muscle  and  the  influence  which  its  disorders 
may  have  exerted  upon  various  organs.  Hence,  chronic  myo- 
carditis renders  prognosis  more  unfavorable  than  an  aortic  or  mitral 
les'on. 

Lesions  of  the  lungs,  aside  from  tuberculosis,  may,  when  they 
disturb  hematosis,  hinder  oxidation.  They  have  also  the  inconveni- 
ence of  disturbing  the  action  of  certain  therapeutic  methods.  Baths, 
even  when  lukewarm,  are  very  badly  borne  by  emphysematous  sub- 
jects. Finally,  when  pulmonary  lesions  influence  the  heart,  they 
produce  through  this  organ  visceral  disturbances  the  importance  of 
which  we  are  about  to  consider. 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASE8.     \ 

Lesions  of  the  kidneys  notwithstanding  thai  they  hinder  organic 
depuration,  do  nol  render  prognosis  very  unfavorable.  No  doubl  we 
often  see  a  Bright's  patienl  succumb  to  an  Lnfectiou  complication, 
suppuration,  erysipelas,  or  pneumonia)  bu1  this  is  al  the  last  period. 
When  the  individual  is  still  resistanl  he  endures  well  an  intercurrent 
infection,  notably  erysipelas.  Lesions  of  the  liver  are  of  greater  con- 
sequenee,  bni  we  ninsi  make  an  importanl  distinction  analogous  to 
Mint  which  we  luive  :i.dinii led  with  reference  to  the  heart.  It  U  nol 
the  extent  or  the  topography  of  the  sclerotic  lesions,  bu1  the  condi- 
tion of  the  hepatic  cells  thai  is  to  be  considered.  A  hypertrophic 
biliary  sclerosis  does  not  prevenl  the  favorable  evolution  of  erysip- 
elas; an  atrophic  sclerosis  renders  the  prognosis  quite  serious  The 
same  is  true  of  diffuse  steatosis  of  the  liver,  as  may  be  observed  in 
alcoholic  individuals.  The  lesion  of  I  lie  cells  explains  the  develop- 
ment of  nervous  accidents,  notably  delirium  tremens,  and  accounts 
for  the  fatal  termination.  It  is  well  to  bear  in  mind,  however,  thai 
hepatic  lesions,  even  when  extensive,  sometimes  remain  latent.  <  m 
the  occasion  of  an  intercurrent  infection  symptoms  of  hepatic  insuf- 
ficiency may  become  manifest.  Affections  of  the  stomach  and  intes- 
tine may  favor  or  hinder  various  infectious  lesions.  Hence,  the  great 
service  of  gastrointestinal  antisepsis  in  the  therapeutics  of  the  most 
varied  infections.  It  may  also  be  stated  that  predisposition  plays  a 
very  important  role  in  the  development  of  grave  nervous  manifesta- 
tions, and  thus  accounts  for  the  persistence  or  the  appearance  of 
certain  disorders  which  may  persist  after  recovery. 

General  Rules  of  Prognosis.  It  is  evidently  impossible  to  lay 
down  general  rules  of  prognosis.  We  have  mentioned  the  principal 
questions  which  the  clinician  has  to  solve.  We  may  explain  the 
method  by  an  example.  Let  us  suppose  that  we  are  dealing  with  a 
case  of  pneumonia.  Examination  of  the  lungs  is  of  prime  importance 
for  diagnosis,  but  not  so  for  prognosis.  It  is  undoubtedly  interesting 
to  know  the  extent  of  the  hepatized  zone,  which  may  be  judged  by 
the  extent  of  the  tubal  murmur:  but  a  more  important  element  to 
be  considered  is  the  condition  of  the  parts  surrounding  the  morbid 
focus  and  the  extent  and  intensity  of  concomitant  congestion.  The 
other  organs  are  to  be  considered  more  than  the  lungs.  Examination 
of  the  urine,  of  the  liver,  and  especially  of  the  heart,  is  of  chief 
importance  in  the  diagnosis.  An  excessive  acceleration  of  the  heart- 
beats, their  weakness,  and  the  appearance  of  fetal  rhythm  must  guide 
both  prognosis  and  therapeutics.     Moreover,  we  must  determine  the 


640  INFECTIOUS  DISEASES. 

constitutional  ground  upon  which  this  pneumonia  evolves,  because, 
with  the  same  lesion  and  with  the  same  influence  of  the  lesion  upon 
the  other  organs  the  prognosis  differs  according  as  the  case  is  that 
of  a  young  or  old,  robust  or  debilitated,  temperate  or  alcoholic  indi- 
vidual. 

When  all  these  problems  have  been  solved  the  task  of  the  physi- 
cian is  not  yet  over.  Prognosis  must  answer  the  following  three 
questions:  1.  What  will  be  the  termination  of  the  present  disease? 
2.  What  is  its  bearing  upon  the  future  of  the  patient?  3.  Of  what 
importance  is  it  for  his  descendants?  It  should,  therefore,  be  deter- 
mined whether  the  disease  will  be  cured  without  leaving  any  appre- 
ciable traces  and  whether  some  disturbances  will  persist  in  conse- 
quence. It  should  be  decided  whether  relapses  or  recurrences  are 
apt  to  take  place,  and  whether  they  can  possibly  be  guarded  against. 
It  should  also  be  predicted  whether  there  will  be  any  sequela?  in  the 
remote  future,  or  whether  the  descendants  of  the  patient  will  be  liable 
to  degeneration  or  sickness.  Along  with  the  prognosis  of  the  individual 
the  prognosis  of  the  race  must  be  laid  down.  Then,  and  then  only, 
has  the  physician  answered  all  the  questions  which  incessantly  meet 
him  on  confronting  each  patient. 

In  establishing  the  rules  of  prognosis  we  have  depended  upon  quite 
simple  clinical  procedures.  As  a  matter  of  fact,  laboratory  proced- 
ures are  in  this  respect  of  little  importance.  It  was  for  a  time  believed 
that  bacteriology  would  supplant  clinical  observation.  The  study 
of  diphtheria  led  to  the  erroneous  conclusion  that  examination  of 
cultures  enabled  one  to  determine  the  gravity  of  angina,  even  in  the 
absence  of  clinical  observation  of  the  patient.  If  the  diphtheria  was 
found  to  be  uncomplicated,  and  if  the  bacillus  developed  upon  the 
serum  medium  was  not  too  long,  the  prognosis  was  favorable.  If, 
on  the  contrary,  the  bacillus  was  long  and  mixed  with  numerous 
streptococci,  the  prognosis  was  grave.  Although  such  correspon- 
dence may  at  times  be  observed,  it  is  far  from  being  the  rule,  and 
cannot  replace  examination  of  the  sick  or  even  modify  the  prognosis 
based  upon  clinical  observation.  We  likewise  believe  that  no  prac- 
tical information  can  be  derived  from  inoculations  into  animals. 
Apart  from  the  difficulties  of  the  method,  the  results  are  too  variable 
to  be  taken  as  a  basis  of  prognosis.  A  microbe  virulent  for  man  not 
infrequently  proves  inoffensive  for  animals,  and  vice  versa.  Finally, 
P.  Courmont  has  recently  proposed  an  ingenious  method  of  serum 
prognosis  based  upon  the  intensity  of  the  agglutinating  reaction. 


DIAGNOSIS  AND  PROGNOSIS  OF  INFECTIOUS  DISEASES,    04] 

This  method  is  evidentlyveryinteresting  and  perfectly  rational,  ince 
it  is  founded  upon  the  appreciation  of  the  organic  reaction  again  I 
the  infection,  but  it  has  thus  far  been  applied  to  typhoid  fever  alone, 
and  while  it  may  render  some  service,  it  is,  like  all  other  laboratory 
procedures,  loo  complex  and  delicate  to  enter  into  currenl  practice. 

we,  therefore,  conclude  thai  prognosis  even  more  than  diago 
should  be  based  upon  simple  procedures,  upon  an  attentive  exam- 
ination of  the  patient,  and  minute  and  complete  amly  i  of  the  di-- 
turbances  which  he  presents,  As  for  diagnosis,  so  for  prognosis:  Jt 
is  not  by  a  sort  of  divining  power  Ihnl  the  physician  succeeds  in 
solving  the  problems  presenting  themselves  with  each  case,  but 
simply  by  a  profound  study  of  pathology  and  long  clinical  experience. 


4L 


CHAPTER    XXII. 

THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

General  Considerations  on  the  Therapeutics  of  Infections.  Toxic  and  Therapeutic 
Equivalents  of  Medicines.  Action  of  Medicines  upon  Normal  and  Infected  Indi- 
viduals. Principal  Therapeutic  Methods  Employed  in  Infections.  Antiseptic 
Method.  Phvsical  Agents.  Chemical  Antiseptics.  Determination  of  the  Antiseptic 
Power  of  Medicines.  Choice  of  Antiseptics.  Antisepsis  of  the  Skin.  Antisepsis 
of  the  Genital  and  Urinary  Organs.  Antisepsis  of  the  Mouth  and  Nose.  Treatment 
of  Purulent  Rhinites.  Antisepsis  of  the  Respiratory  Passages.  Antisepsis  of  the 
Alimentary  Canal.  Importance  of  Insoluble  Antiseptics.  Antisepsis  of  Serous 
Membranes.  Intestinal  Antisepsis.  Employment  of  Peroxide  of  Hydrogen. 
General  Antisepsis.  Antitoxinic  Method.  Specific  Medication :  Cinchona,  Mercury, 
Iodine,  and  Salicylic  Acid.  Bacteriothcrapy.  Employment  of  Sterilized  Cultures  of 
Streptococcus  and  B.  prodigiosus.  Attempts  in  Cancer  and  Eupus.  Tuberculin. 
Mallein.  Serumtherapy.  General  Principles.  Various  Applications  of  Serum- 
therapy.  Serumtherapy  against  Cholera,  Colon  Bacillus,  Diphtheria,  Leprosy, 
Glanders,  Bubonic  Plague,  Pneumococcosis,  Proteobacillosis,  Pyocyanobacillosis, 
Staph}dococcosis,  Streptococcosis,  Puerperal  Fever,  Tetanus,  Tuberculosis,  Typhoid 
Fever,  Eruptive  Fevers,  Vaccinia,  Variola,  and  Hydrophobia.  Prophylactic  Injec- 
tions of  Serum.  Accidents  Ascribable  to  Serumtherapy :  Cutaneous  and  Articular 
Manifestations;  Fever;  Albuminuria,  Hemorrhages,  and  Nutritional  Disturbances. 
Post-serum  Therapic  Hysteria.  Prognosis  of  Serumtherapic  Accidents.  Mode  of 
Action  of  Therapeutic  Serums.     Conclusions. 

By  their  natural  evolution,  acute  infections  tend  toward  recovery. 
The  duty  of  the  physician  is  to  observe  the  procedures  resorted  to 
by  nature,  and,  thus  inspired,  to  direct  the  morbid  reactions  and 
stimulate  or  restrain  them,  as  the  case  may  be. 

The  organism  endeavors  to  destroy  and  expel  infectious  germs  and 
to  neutralize  and  eliminate  toxins.  Similarly  our  therapeutic  meas- 
ures should  be  directed  to  the  accomplishment  of  these  four  purposes. 
Various  procedures  which  not  infrequently  differ  from  those  em- 
ployed by  nature  may,  however,  be  utilized  in  therapeutics. 

To  combat  the  animate  agent  which  gives  rise  to  infection  is  to 
practise  etiological  medication.  To  deal  with  the  toxins  through 
which  the  morbific  germ  acts  is  to  practise  pathogenic  or  physio- 
logical therapeutics,  as  the  case  may  be. 

Etiological  medication  is  the  application  of  the  old  adage :  Sublata 
causa  eff edits  tollitur.  It  finds  its  formula  in  the  antiseptic  method. 
The  ideal  would  be  the  possession  of  substances  which  would  destroy 


THERAPEUTICS  OF  INFE0TI0U8  DISEASE  $43 

fche  germs  and  I"'  inoffensive  for  the  patient.  Unfortunately,  here 
is  fche  stumbling-block.  Neverthele  .  il  ii  po  ible,  with  certain 
precautions,  to  realize  antisepsis  in  surface  wounds  and  at  time  in 
fistulous  tracts.  Kvcn  in  wounds,  certain anti  eptic  exeii  an  irritant 
action.  They  diminish  the  resistance  of  the  cells,  and,  in  spite  of 
their  incontestable  action  upon  the  microbe,  they  favor  rather  than 
hinder  infection.  At  present ,  therefore,  the  tendency  i  to  substitute 
asepsis  for  antisepsis,  and,  when  antiseptic  substance!  are  employed, 
care  is  taken  to  use  weak  solutions.  Willi  these  precautions  the 
results  are  often  satisfactory,  provided,  however,  the  antiseptics  are 
frequently  changed.  When  any  one  of  them  is  used  for  ;i  long  period 
of  time,  the  action  is  weakened  through  habit. 

The  abortive  method,  which  is  calculated  to  arresl  ;ni  infection  at 
its  beginning,  belongs  to  the  antiseptic  method,  and  it  bs  probable 
that  specific  medication  should  also  he  included  in  ih«'  3ame  group. 

We  are  acquainted  with  certain  substances  which  aires)  the  course 
of  certain  infections.  It  is  hardly  necessary  to  mention  the  action 
of  quinine  in  malaria,  of  mercury  and  the  iodides  in  syphilis,  and  of 
the  salicylates  in  rheumatism.  The  germicidal  serums  also  belong  to 
this  group.  They  represent  the  specific  antiseptics  par  excellence, 
possessing  a  selective  action  in  destroying  certain  microbes  and  being 
powerless  against  allied  germs. 

The  microbe,  as  we  have  repeatedly  stated,  is  not  the  sole  cause 
of  an  infectious  disease.  Auxiliary  and  predisposing  causes  often 
come  to  its  assistance.  The  therapeutist  must  take  them  into  con- 
sideration. His  method  is  equally  etiological  when  he  struggles 
against  the  various  conditions  which  favor,  maintain,  or  aggravate 
infection.  He  can  fulfil  therapeutic  indications  by  means  of  diet, 
hygiene,  and  at  times  through  special  medication  or  surgical  inter- 
vention. Furunculosis  ma}-  be  cured  by  combating  the  digestive 
disturbances  which  produce  or  sustain  it:  suppuration  may  be 
arrested  by  extirpating  the  foreign  body  which  is  found  in  the  mor- 
bid focus.  While  in  these  cases  medication  is  not  directed  against 
the  primary  cause,  it  none  the  less  deserves  to  be  considered  as 
etiological  medication . 

Pathogenic  medication  is  that  which  combats  the  harmful  action 
of  the  pathogenic  agent  upon  the  organism.  Bacteria  act  mainly  by 
their  toxins.  Therefore,  all  treatment  directed  against  bacterial 
poisons  we  consider  as  pathogenic.  In  many  cases,  however,  patho- 
genic treatment  is  confounded  with  physiological  or  naturalistic 


644  ISFECTIO  US  DISEASES. 

treatment,  which  is  intended  to  act  against  toxins,  following  the 
processes  which  the  organism  emploj^s  for  the  same  purpose.  The 
distinction  is  in  fact  of  little  importance,  for  it  may  be  said  that  the 
struggle  against  infections  conducted  by  the  organism  is  carried  on 
on  lines  of  pathogenic  therapeutics.  In  support  of  this  assertion  it 
will  suffice  to  cite  serumtherapy.  We  have  stated  above  that  certain 
germicidal  serums  which  destroy  microbes,  or  at  least  exert  upon 
them  a  harmful  action,  represent  an  etiological  method  of  treatment. 
The  serums  which  neutralize  the  effect  of  toxins  are  more  important. 
When  we  employ  them  against  an  infection,  when,  for  instance,  we 
inject  antidiphtheritic  serum  into  a  patient,  we  practise  pathogenic 
as  well  as  naturalistic  therapeutics — pathogenic,  because  we  combat 
the  mode  of  action  of  the  cause;  naturalistic,  because  we  are  guided 
by  the  reactionary  mode  of  the  diseased  organism.  In  fact,  we  know 
that,  in  order  to  combat  the  microbic  poison,  the  organism  secretes 
an  antitoxin.  Through  the  agency  of  therapeutics  we  furnish  to  the 
organism,  from  the  very  start  of  the  disease,  the  protective  substance 
which  it  needs.  We  realize  sooner  what  the  organism  would  realize 
later.  Thus  we  save  time  by  arresting  bacterial  intoxication  at  a 
moment  when  its  effects  are  still  reparable. 

It  is  not  the  bacterial  poisons  alone,  however,  that  are  to  be 
reckoned  with  in  infections.  The  synergy  which  unites  all  the  parts 
of  the  organism  spreads  the  disturbances  throughout  the  entire 
economy.  Hence  the  secondary  autointoxications,  which  should 
never  be  lost  sight  of.  In  many  cases  procedures  directed  against 
these  poisons  are  nearly  the  same  as  those  employed  against  toxins. 
In  fact,  an  attempt  may  be  made  to  neutralize  the  noxious  substances 
formed  by  the  organism  or  to  stimulate  the  organs  charged  with  the 
function  of  destroying  them,  or  an  effort  may  be  made  to  favor  their 
elimination. 

In  order  to  neutralize  the  autogenic  poisons  the  oxidizing  method, 
which  seems  to  act  upon  the  microbic  as  well  as  upon  the  animal 
toxins,  is  generally  employed.  When  it  is  desired  to  stimulate  the 
organs  concerned  in  the  destruction  of  poisons,  use  should  be  made 
of  various  substances  capable  of  stimulating  the  cells,  notably  those 
of  the  fiver.  The  role  played  by  alimentation  has  already  been 
referred  to.  It  will  suffice  to  add  that  ether,  in  small  doses,  exerts 
a  very  manifest  action  upon  this  gland. 

The  liver  acts  upon  animal  and  certain  microbic  toxins,  and,  in 
addition,  possesses  the  power  of  destroying  a  great  number  of  bac- 


THEBAPEUTI08  OF  INFECTIOUS  DISEASES.  646 

fceria.    Thus  the  many  indications  to  which  fchi    therapeutic  method 

responds  are  evidenl . 

The  same  complexity  in  effect  appear  r  ith  regard  to  elimination. 
The  simplest  procedure  seems  to  be  represented  by  blood-letting. 
The  flow  of  the  blood  carries  away  a  certain  amounl  of  toxins.  Jn 
reality,  however,  the  action  of  blood-letting  is  very  complex,  beci 
at  the  same  time  thai  the  constitution  of  the  blood  is  modified,  the 
exchanges  .-ire  slimuhinl  and  the  work  of  the  heari  i-  diminished. 
Blood-letting  docs  noi,  therefore,  represenl  a  simple  antitoxic 
method. 

The  elimination  of  toxins  and,  coincidently,  microbes  may  like 
be  favored  by  stimulating  the  emunctories,  the  digestive  tract,  the 
skin,  and,  particularly,  the  kidneys.  Lavage  of  the  stomach  and 
intestine,  the  administration  of  emetics  and  purgatives  serve  to  <-.irvy 
away  the  noxious  elements  which  originate  in  the  alimentary  canal 
or  are  thrown  into  it.  Certain  drugs  may  increase  the  activity  of  the 
emunctories.  Sudorifics,  diuretics,  and  tepid  beverages  are  often 
employed.  In  the  treatment  of  acute  infection-,  however,  physical 
procedures  are  generally  preferred.  Heat  or  cold  are  called  into  play, 
as  the  case  may  be.  Dry  heat  favors  sweating.  Moist  heat  stimu- 
lates or  quiets  the  nerves.  Lastly,  a  cold  bath  acts  not  so  much  by 
dissipating  the  heat  of  the  body  as  by  mochTying  the  dynamic  state 
of  the  organism  by  means  of  the  nervous  reactions  to  which  it  gives 
rise.  It  acts  upon  the  general  nutrition,  upon  the  activity  of  the 
liver,  and  especially  upon  the  urinary  secretion,  which  it  increases 
considerably. 

It  was  hoped  for  a  time  that  it  would  be  possible  to  effect  rapid 
depuration  of  the  organism  by  intravenous  or  subcutaneous  injec- 
tions of  artificial  serum.  While  more  profound  study  has  demon- 
strated the  excellent  effects  of  this  form  of  medication  in  the  treat- 
ment of  acute  infections,  it  has  likewise  established  that  its  action 
is  very  complex  and  that  it  affects  the  nervous  system  and  general 
nutrition  rather  than  the  emunctories. 

It  is  thus  seen  that  most  of  the  procedures  above  indicated  are  far 
less  simple  than  would  at  first  appear.  They  act  mostly  upon  the 
organism  and  stimulate  the  general  reactions.  The  injections  of 
antitoxic  serum  or  salt-water  give  rise  to  cellular  proliferations  which 
must  favor  the  defense  of  the  organism.  Therefore,  not  only  humoral 
modifications  are  produced,  but  the  figurate  elements  are  likewise 
acted  upon.    Besides  the  general  reactions  of  the  organism,  the  local 


646  INFECTIO  US  DISEASES. 

reactions  which  appear  at  the  point  invaded  by  pathogenic  agents 
must  be  considered. 

According  to  circumstances,  local  inflammation  must  be  stimu- 
lated, checked,  or  diverted.  Even  acute  manifestations  may  be  stim- 
ulated. Thus,  one  of  the  best  treatments  of  erysipelas  or  phlegmons 
consists  in  very  hot  applications.  The  reaction  of  the  organism  is 
thus  increased  and,  consequently,  rendered  more  rapidly  efficacious. 
The  phlogistic  method  is  far  oftener  resorted  to  in  the  case  of  torpid 
lesions.  Certain  suppurating  foci,  certain  tubercular  lesions,  or 
ulcerations  of  any  description,  are  treated  by  hot  applications,  scari- 
fications, and  cauterizations.  These  procedures  bring  about  recovery 
by  awakening  an  inflammation  which  had  prematurely  ended.  In 
other  instances  this  effect  is  secured  by  means  of  toxic  substances. 
Potassium  canthariclate  and  tuberculin  stimulate  atonic  tubercular 
lesions.  Or  wre  may  act  by  producing  a  microbic  inflammation.  We 
have  sufficiently  studied  this  question  in  connection  with  microbic 
associations  and  shown  notably  the  curative  role  of  erysipelas. 

In  cases  in  which  local  reaction  is  too  intense,  it  is  evidently 
necessary  to  moderate  inflammation.  This  is  particularly  indicated 
wrhen  the  lesion  occupies  an  important  organ  and  threatens  life  by 
disturbing  its  function.  It  is  usual  to  apply  refrigerants  and  espe- 
cially ice  continuously  over  the  cardiac  region,  the  abdomen,  and 
the  head  in  cases  of  pericarditis,  peritonitis,  or  meningitis,  respec- 
tively. Peri-inflammatory  or  pre-inflammatory  congestion  is  also 
combated  by  blood-letting,  antiphlogistics,  and  vasomotor  medi- 
cines. While  nitrites  are  utilized  to  stimulate  reactions,  vasocon- 
strictors, such  as  ergotin,  are  employed  to  restrain  them.  Finally, 
a  derivation  may  also  be  brought  about.  When  an  inflammation  is 
too  intense,  a  revulsion  at  a  more  or  less  distant  point  can  be  induced. 
This  may  sometimes  be  in  the  area  of  the  skin  corresponding  to  the 
diseased  region,  where  thermocauterization  or  mustard  plaster  is  to 
be  applied.  On  other  occasions  the  digestive  canal  may  be  acted 
upon,  for  example,  by  means  of  purgatives.  Thus  a  sort  of  metas- 
tasis is  artificially  produced. 

We  cannot,  therefore,  in  an  exclusive  manner  assert  that  reactions 
must  be  combated  or  stimulated.  It  is  only  necessary  to  remember 
that  inflammatory  actions  are  always  useful.  They  represent  a 
means  of  defense.  It  is  to  be  noted,  however,  that  their  intensity 
may  exceed  the  object.  We  may  then  conclude  that  reaction  must 
sometimes  be  combated,  often  stimulated,  and  always  directed. 


THERAPEUTICS  OF  INFECTIOUS  DISEA8E8.  <;}? 

Although  the  medications,  the  general  laws  of  which  we  have  jusl 
indicated,  are  fche  most  rational,  ymptomatic  therapeutic  mu  •  not 
be  despised.  The  latter  consists  simply  in  remedying  immediate 
accidents,  in  combating  certain  disturbance  without  reascending  to 
their  cause  or  point,  of  departure.  Although  it  musl  frequently  be 
considered  as  an  acknowledgment  of  our  ignorance,  this  method  is 
at  limes  the  only  possible  and  even  the  only  admissible  one.  When 
we  are  confronted  by  accidents  which  threaten  lifewe  musl  resorl  to 
urgent  medication  directed  againsl  the  disorder  observed  without 
looking  for  its  origin.  When  the  physician  is  called  to  the  bedside 
of  a  patient  who  is  suffocating,  and  he  has  recognized  by  the  char- 
acters of  respiratory  embarrassment  that  i1  is  dependenl  upon  laryn- 
geal stenosis,  his  lirsi  thought  should  be  to  re-establish  the  coin 
the  air  and  immediately  perform  tracheotomy.  Be  may  subse- 
quently investigate  the  cause  of  the  stenosis. 

Symptomatic  therapeutics  mayserve  as  an  auxiliary, and  i-  then 
perfectly  justifiable.  A  patient  suffering  from  syphilitic  cephalalgia 
must  receive  specific  treatment.  As,  however,  the  latter  requires 
several  days  to  produce  its  effects,  symptomatic  medication  is  at  the 
same  time  to  be  resorted  to  in  order  to  relieve  the  nocturnal  exacer- 
bations of  pain  and  procure  rest  to  the  sufferer.  To  this  end,  along 
with  60  to  90  grains  (1  to  6  grams)  of  potassium  iodide  directed  to 
the  syphilitic  element,  some  hypnotic  should  be  prescribed  to  relieve 
the  headache. 

It  is  perfectly  rational  symptomatic  medication  to  prescribe  opium 
for  cough,  atropine  for  sweating,  enemas  or  purgatives  for  constipa- 
tion, and  analgesics  for  pain.  In  all  these  cases  symptomatic  medi- 
cation assists  therapeutics.  It  is,  therefore,  perfectly  justifiable.  On 
the  other  hand,  however,  it  is  an  avowal  of  our  impotence  if  we  are 
contented  with  treating  a  symptom  because  we  are  unable  to  recog- 
nize its  mechanism  or  trace  it  to  its  cause. 

Among  the  symptoms  which  most  frequently  call  for  treatment, 
fever  deserves  special  mention.  The  rise  of  temperature  is  painful 
for  the  patient,  it  causes  anxiety  to  the  family,  and  preoccupies  the 
mind  of  the  physician.  Apprehension  is  felt  that  hyperthermia  will 
give  rise  to  serious  accidents  if  too  intense  and  allowed  to  persist. 
Moreover,  since  the  use  of  the  thermometer  has  become  a  daily 
practise,  it  is  one  of  the  disturbances  which  is  most  readily  detected. 
There  is,  therefore,  an  inclination  to  direct  all  efforts  against  it.  This 
inclination  is  expressed  by  the  introduction  into  therapeutics  of  a 


648  IXFECTIO  US  DISEASES. 

prodigious  number  of  febrifuges.  But  it  seems  to  be  demonstrated 
to-day  that  the  cellular  lesions  which  were  once  attributed  to  fever 
depend  rather  upon  the  toxic  cause  which  engenders  fever,  and  that 
hyperthermia  is,  in  reality,  not  so  dangerous.  At  any  rate,  most  of 
the  febrifuges,  excepting  specific  ones,  act  upon  the  mechanism  and 
not  upon  the  cause.  As  a  rule,  they  hinder  salutary  reactions, 
diminish  oxidations,  and  consequently  exert  an  unfavorable  in- 
fluence. Exception  is  to  be  made  only  of  cold  bathing,  which  alone 
is  rational,  since  it  lowers  the  temperature  by  abstracting  heat.  In 
connection  with  pathological  physiology,  we  have  shown  that,  in 
fever,  the  dissipation  of  heat  is  increased.  Cold  bathing  further 
increases  and  thereby  completes  the  work  of  defense  undertaken  by 
the  organism;  it  thus  enters  into  the  domain  of  natural  medication. 

General  Rules  of  Therapeutics  in  Infections.  The  therapeutics 
of  infectious  diseases  is  based  upon  clinical  observation  and  experi- 
mental research.  Formerly  attempts  were  first  made  upon  diseased 
men.  The  old  physicians,  led  by  theoretical  ideas  which  were  often 
erroneous,  or  assisted  b}^  some  happy  coincidence,  tried  a  great  num- 
ber of  medicinal  substances.  Some  of  these,  having  proved  really 
efficacious,  are  still  employed.  At  times  we  utilize  them  without 
knowing  exactly  by  what  mechanism  they  act.  Tradition  having 
established  their  role,  we  cannot  blame  empiricism  directing  this 
course  of  action.  Sometimes  experimentation  immediately  demon- 
strated the  mode  of  action  of  the  medicine  or  explained  and  justified 
its  emplojmient.  Formerly  experimentation  upon  animals  followed 
the  application  to  man.  At  the  present  day  therapeutics  must  adopt 
a  reverse  course  and  always  begin  with  experimental  study.  The 
latter  informs  us  as  to  the  toxic  and  pharmacodynamic  action  of  the 
medicine.    It  therefore  has  a  double  object. 

In  order  to  determine  the  toxic  equivalent  of  a  substance,  it  is 
necessary  to  experiment  upon  animals  of  different  species.  We  can- 
not be  too  cautious  when  acting  upon  man.  The  fatal  close  is  deter- 
mined by  intravenous  injection,  and  for  certain  medicines  the  dose 
which  is  immediately  fatal  and  that  which  is  ultimately  so  should 
be  ascertained.  It  is  necessary  to  know  that  certain  substances, 
even  when  injected  into  the  veins,  produce  no,  or  only  slight,  dis- 
turbances. If,  however,  the  dose  is  increased,  the  animal  dies  a  few 
seconds  after  injection  or  even  while  the  toxic  substance  is  still  being 
introduced.  With  certain  substances,  if  the  intravenous  injection  is 
arrested  at  the  moment  when  the  fatal  dose  is  approached,  the 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  649 

symptoms  disappear  and  the  animal  recovers.  However,  auch  i-  not 
always  the  case.  There  is  often  a  period  of  latency  during  which 
the  animal  appears  to  be  in  good  health.  After  a  variable  length 
of  time  disorders  are  produced  and  terminate  in  death.  The  poison 
did  not  act  immediately,  and  perhaps  it  underwenl  previous  b 
formation  within  the  organism,  lie  thai  at  it  may,  the  do  e  which 
is  tardily  fatal  is  often  considerably  smaller  than  the  one  immediately 
fatal,  and,  for  the  physician,  this  is  a  poinl  of  greaf  consequence. 

As  intravenous  injection  of  medicines  is  seldom  employed,  it  is 
indispensable,  after  studying  the  toxicity  of  the  substance*  injected 
into  the  blood,  to  investigate  their  action  when  they  are  introduced 
by  other  channels,  notably  beneath  the  skin  or  into  the  alimentary 
canal.  The  role  of  absorption,  the  influence  of  transformations  which 
may  occur  within  the  gastrointestinal  cavity,  in  contact  with  ali- 
ments, secretions,  and  microbes  which  multiply  there,  may  modify 
the  composition  and  consequently  the  action  of  medicine-:.  When 
absorption  has  taken  place,  the  substance,  before  reaching  the  points 
upon  which  it  acts,  passes  through  certain  glands  which  may  further 
modify  its  composition  or  its  action.  Among  the  latter  are  the  liver 
and  lungs. 

These  are  sufficient  reasons  for  multiplying  the  experiments  and 
injecting  the  poison  by  the  most  varied  channels.  It  does  not  suffice, 
however,  simply  to  notice  the  effects  of  a  single  dose.  In  general, 
the  physician  prescribes  a  medicine  for  several  days  in  succession. 
The  experimenter  must,  therefore,  administer  the  substance  for  a 
certain  length  of  time,  and,  if  no  disturbance  results,  he  must  not  yet 
declare  the  substance  to  be  harmless.  He  must  observe  the  animals 
and  kill  some  of  them  in  order  to  learn  whether  there  are  pro- 
duced in  their  organs  lesions  unexpressed  by  any  symptom  and 
which  can  be  determined  onty  by  histological  examination. 

These  preparatory  studies  are  very  tedious  and  delicate.  It  seems 
to  us,  however,  that  they  are  indispensable  when  it  is  desired  to 
make  therapeutic  application  to  human  beings.  It  is  to  be  noted, 
however,  that  these  first  investigations  teach  us  only  the  dangerous 
and  harmless  doses.  After  determining  these  first  points,  namely, 
after  solving  the  toxicological  problem,  the  pharmacodynamic  study 
is  to  be  undertaken.  Assisted  by  all  the  modern  scientific  data,  an 
inquiry  into  the  modifications  of  the  medicine  within  the  organism, 
its  channels  of  elimination,  its  action  upon  the  fluids,  tissues,  and 
organs  ma}'  be  made.    In  this  connection,  chemical  analysis  on  the 


650  INFECTIOUS  DISEASES. 

one  hand,  and  on  the  other  physiological  analysis  and,  notably,  the 
graphic  method,  must  intervene. 

The  rules  just  referred  to  are  general  rules  applicable  to  all  thera- 
peutic studies.  When  the  treatment  of  infections  is  reached  these 
rules  require  to  be  completed  with  some  particular  data. 

Since  we  can  produce  in  animals  a  great  number  of  infectious  dis- 
eases we  must  no  longer  pursue  our  studies  by  operating  upon 
healthy  but  upon  infected  animals. 

The  necessity  of  investigations  of  this  sort  appears  when  it  is 
believed  that  a  medicine  capable  of  curing  a  disease  has  been  found. 
It  is  then  necessary  to  inoculate  a  certain  number  of  animals,  some  of 
which  are  to  be  kept  as  controls  and  others  to'receive  the  medicinal 
substances.  The  results  thus  obtained  are  of  great  value,  since 
experimental  infection  is  always  simpler  than  a  spontaneous  infec- 
tion. It  is  monomicrobic,  while  in  man  the  disease  often  results  from 
an  association  of  microbes.  The  treatment  may  be  begun  as  soon 
as  is  desired,  while  in  spontaneous  infection  the  first  symptoms  are 
often  belated  and  appear  a  long  time  after  contamination.  Lastly, 
the  use  of  control  animals  gives  undeniable  value  to  experimental 
results,  while  in  clinical  experience  we  may  clearly  see  what  is  pro- 
duced as  a  result  of  the  treatment,  but  we  do  not  know  what  would 
happen  in  case  of  abstention. 

Nevertheless,  we  must  not  conclude  that  the  successes  are  the 
same  in  both  cases,  for  the  reason  that  clinical  cases  are  complex,  and 
treatment  is  often  commenced  too  late,  or  the  organism  is  affected 
by  taints  or  previous  lesions.  Clinical  observation  must  pronounce 
final  judgment,  and,  too  often,  it  establishes  an  apparent  antagonism 
between  practical  application  and  experimental  results. 

When  it  is  desired  to  determine  the  action  of  antimicrobic  or  anti- 
toxic substances  the  pharmacodynamic  action  is  often  discarded 
and  an  attempt  is  made  to  solve  the  following  three  problems :  What 
is  the  action  of  the  substance  upon  the  microbe  or  the  toxin  outside 
the  organism?  What  is  its  toxic  action  upon  the  healthy  animal? 
What  is  its  curative  action  upon  the  diseased  animal — i.  e.,  upon  the 
infected  or  intoxicated  animal  ? 

The  rules  which  govern  the  solution  of  the  last  two  questions  are 
the  general  rules  which  we  have  already  exposed.  As  to  the  first 
problem,  if  the  question  concerns  an  antiseptic  substance,  it  is  cus- 
tomary to  investigate  the  effect  of  artificial  media  upon  the  vegeta- 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8ES.  <;.,] 

tive  property  of  the  microbe,  [noculations  into  animals  should  be 
next  undertaken,  for  microbes  which  are  o  altered  a*  to  no  longer 
develop  in  a  culture  bouillon  may  sometimes  be  still  sufficiently 
active  to  vegetate  within  the  organism.  On  the  other  hand,  microbes 
which  are  incapable  of  overcoming  the  resistance  of  the  economy  may 
still  be  able  to  live  in  inert  media.  The  greal  principle  of  atten- 
uation of  viruses  is  based  upon  this  fact. 

When  antitoxic  substances  are  under  study,  experimentation  i- 
the  only  method  which  reveals  the  modifications  produced.  The 
toxin  and  the  antitoxin  are  injected  into  the  animals  simultaneously 
and  successively.  These  principles  are  daily  utilized  in  the  study  of 
therapeutic  scrums. 

It  is  certain  that  the  method  furnishes  excellent  indications. 
Although,  in  this  case,  experimentation  approaches  clinical  obser- 
vation as  nearly  as  possible,  the  facts  do  not  and  cannot  altogether 
correspond.  The  experimental  results  obtained  with  serums  are 
always  more  brilliant  than  those  observed  clinically.  The  reason  is 
that  clinical  facts  are  always  complex.  Honce,  even  when  a  greal 
number  of  specific  serums  have  been  prepared,  it  will  still  be  neces- 
sary to  resort  to  medicines  intended  to  palliate  certain  disturbances 
and  to  combat  certain  accidents. 

Unfortunately,  the  substances  which  are  used  in  this  case  have 
been  studied  only  upon  healthy  animals.  It  would,  therefore,  be 
interesting  to  repeat  their  study  upon  infected  animals  from  the 
double  standpoint  of  toxicology  and  pharmacodynamics.  It  is  m 
sary,  in  fact,  to  determine  whether  the  medicine  has  the  same 
toxic  property  in  the  diseased  and  the  healthy  animal,  and  whether 
this  toxicity  is  modified  by  the  different  periods  of  the  disease.  It  is 
also  necessary  to  inquire  whether  the  medicine  always  acts  in  the 
same  manner,  whether  infection  does  not  modify  its  mode  of  action. 
Here,  we  believe,  is  a  large  field  open  to  experimenters.  As  few 
researches  have  been  made  upon  this  point,  we  have  believed  it 
would  be  of  interest  to  study  what  becomes  of  the  resistance  of 
animals  through  strychnine  in  the  course  of  anthrax  infection,  and 
then  to  undertake  analogous  researches  with  strychnine  and  chloral 
in  animals  suffering  from  tetanus.  From  our  experiments  we  may 
draw  the  conclusion  that  chloral  may  be  employed  to  palliate  the 
painful  phenomena  produced  by  tetanus,  but  it  is  not  a  truly  cura- 
tive medicine. 


652  INFECTIOUS  DISEASES. 

Antiseptic  Method. 

The  object  of  the  antiseptic  method  is  to  destroy  the  pathogenic 
agents  by  acting  directly  upon  them  and  indirectly  by  modifying 
the  organism.  When  it  is  incapable  of  destroying  these  agents,  it 
opposes  their  multiplication  or  hinders  their  harmful  action.  We 
know  at  present  that  microbes  act  only  by  their  soluble  products. 
The  history  of  antitoxic  substances  which  neutralize  or  diminish 
the  action  of  toxins  may,  therefore,  be  considered  as  supplementary 
to  the  study  of  antiseptics. 

Antisepsis  by  Physical  Agents.  The  indications  of  antisepsis  may 
be  realized  by  procedures  of  a  physical  order.  As  is  known,  heat  is 
the  surest  agent  for  destroying  microbes.  Unfortunately,  although 
it  is  daily  employed  for  sterilizing  inert  substances,  it  is  too  difficult 
to  manage  when  applied  to  the  living  organism.  While  very  hot 
local  applications  hinder  infections ;  they  accomplish  this  simply  by 
modifying  circulation.  They  act  upon  the  microbes  in  an  indirect 
manner.  When,  however,  the  lesion  is  well  circumscribed,  it  is  pos- 
sible to  destroy  it  by  thermocauterization.  Folliculites  are  thus 
cured.  If  the  lesion  is  extensive,  a  red-hot  iron  can  be  used,  as  is 
done  for  certain  phlegmons  and  gangrene.  It  is,  perhaps,  possible 
to  combat  infections  of  serous  membranes  by  very  hot-water  irriga- 
tions. It  is  possible  to  inject  into  the  peritoneum  or  the  veins  of 
animals  salt  water  at  a  temperature  of  122°  F.  (50°  C.)  or  131°  F. 
(55°  C.)  without  any  inconvenience.  We  should  not,  however,  rely 
too  much  upon  these  different  methods,  since  heat  coagulates  albu- 
mins, and  the  minute  particles  thus  formed  protect  the  pathogenic 
agents.  Moreover,  when  it  is  intense,  heat  cannot  be  applied,  except 
to  circumscribed  points,  and,  consequently,  it  acts  upon  a  very 
restricted  area  of  the  diseased  tissue. 

There  are  certain  viruses  which  are  much  more  sensitive  to  heat 
than  the  neighboring  tissues.  Thus  the  investigations  of  Dr.  Aubert 
show  that  100.4°  F.  (38°  C.)  is  sufficient  to  check  the  multiplication 
of  the  bacillus  of  soft  chancre.  At  a  temperature  of  104°  F.  (40°  C.) 
the  microbe  is  killed.  Hence,  by  employing  this  temperature,  which 
is  not  harmful  for  the  tissues,  we  may  rapidly  cure  a  soft  chancre. 
A  variant  of  this  method  consists  in  treating  the  lesion  by  means 
of  overheated  air. 

Microbes  withstand  cold  far  better  than  heat.  Hence,  cold  appli- 
cations, although  they  sometimes  modify  the  vitality  and  the  inflam- 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  853 

matory  react  ions  of  I  Ik:  (issues,  exerl    no  influence  whatever  upon 

the  pathogenic  elements.  When  the  germicidal  action  <>f  the  sun's 
rays  were  revealed,  the  influence  of  lighl  upon  the  cow  e  of  infections 
was  investigated.  The  problem  is  complex,  however,  since  the 
action  exerted  upon  the  organism  and  upon  the  microbei  i  to  be 
taken  into  account,  [nteresting  attempts  bave  neverthelet  been 
made  with  Hie  object  of  utilizing  certain  properties  of  sunlight. 
Finsen  has  become  the  champion  of  Hie  phototherapic  method.  An 
attempt  has  also  been  m;idc  In  cause  patienb  suffering  from  variola 
to  sojourn  in  wards  provided  with  red  glass  window.-.  The  results 
have  not  been  very  encouraging.  On  the  other  band,  quite  remark- 
able results  have  been  obtained  by  treating  lupus  patients  with  coi- 
orcd  sun-rays. 

Antisepsis  by  Chemical  Agents.  Chemical  antiseptics  are 
trcmcly numerous, and  certain  amongthem  were  known  and  employed 
in  olden  times.1  In  the  days  of  Hippocrates  wine  and  aromatic 
oils  and  certain  caustic  iron  and  copper  salts  were  employed  for 
washing  wounds.  The  same  substances  were  much  used  in  the  middle 
ages.  Later,  cinchona  powder,  mercurial,  arsenical,  and  astringent 
preparations,  as  well  as  balsams  and  resins,  came  into  use. 

We  must  come  to  the  time  of  Lister  to  find  a  true  doctrine  of 
antisepsis,  at  least  of  surgical  antisepsis.  Lister,  taking  a>  a  basis 
the  works  of  Pasteur  on  fermentations,  assumed  that  the  air  exer- 
cised a  noxious  influence  upon  wounds  by  virtue  of  the  germs  which 
it  contained  and  deposited  in  the  wounds.  Therefore,  making  use 
of  carbolic  acid,  which  was  already  employed  by  Lemaire,  he  washed 
his  hands  with  a  2\  per  cent,  solution,  immersed  his  instruments  in 
a  stronger  solution  (5  per  cent.),  washed  the  field  of  operation  with 
a  strong  solution,  and  during  the  operation  directed  upon  the  field 
a  spray  of  carbolic  acid .  He  then  introduced  drainage  tubes  sterilized 
by  means  of  carbolic  acid.  Lastly,  after  covering  the  wound  with 
a  protective  bandage,  he  applied  carbolized  gauze  and  impermeable 
mackintosh  tissue. 

At  present  the  principles  laid  down  by  Lister  are  modified  and  his 
procedures  are  abandoned.  The  germs  of  the  air  are  not  feared  as 
they  wrere  formerly.  The  pathogenic  agents  present  upon  the  skin 
of  the  patient  are  more  to  be  feared,  and  especially  those  found  upon 
the  hands  of  the  surgeon  and  his  assistants.    Therefore,  the  spray 

1  Weiss.  Contribution  a  letude  des  niethodes  servant  a  determiner  le  pouvoir  anti- 
septique.     Th&se  de  Paris,  1900. 


65-1  INFECTIOUS  DISEASES. 

was  first  done  awaywith :  next, the  instruments  and  the  dressings  were 
successfully  sterilized  by  heat;  then  the  use  of  antiseptics  was  grad- 
ually abandoned,  and  in  a  word,  asepsis  was  substituted  for  anti- 
sepsis. This  is  at  least  what  is  done  in  surgical  operations  when 
diseased  but  not  infected  parts  are  operated  upon.  When,  on  the 
contrary,  parts  invaded  bj'  pathogenic  germs  are  dealt  with,  anti- 
sepsis is  still  utilized.  It  has  been  recognized,  however,  that  strong 
antiseptics  are  to  be  avoided,  because  of  their  caustic  action,  which 
is  more  harmful  to  the  tissues  than  to  the  microbes.  In  most  cases 
it  is  sufficient  to  resort  to  profuse  lavage  with  boiled  water,  which 
acts  mechanically  by  carrying  aw^  the  germs  and  their  toxins  as 
well  as  the  degenerated  cells  contained  in  the  morbid  focus. 

"While  antisepsis  has  lost  its  first  importance  in  surgery,  it  is  still 
held  in  great  esteem  in  medicine.  Attempts  have  been  made  to  kill, 
at  least  partially,  the  germs  swarming  in  the  digestive  canal  and 
those  which  may  invade  the  respiratory  or  urinary  apparatus.  Even 
general  antisepsis  of  the  organism  has  been  aimed  at  by  some  prac- 
titioners. It  is,  therefore,  important  to  have  at  one's  disposal  a 
certain  number  of  antiseptic  substances. 

An  antiseptic  must  fulfil  certain  general  conditions  and,  according 
to  the  use  for  which  it  is  destined,  possess  particular  properties.  The 
general  properties  of  all  antiseptics  are  the  following :  to  be  harmful 
for  the  morbid  germs ;  to  be  harmless  for  the  animal  cells  with  which 
it  comes  in  contact ;  not  to  form  with  the  organic  elements  combina- 
tions which  render  them  inoffensive  for  microbes;  not  to  coagulate 
albumins  the  particles  of  which  protect  the  bacteria. 

The  particular  properties  may  be  diametrically  opposed  according 
to  the  case.  According  as  we  have  to  sterilize  a  closed  cavity  or  a 
surface,  to  act  upon  a  limited  area,  or,  on  the  contrary,  to  extend 
the  germicidal  action  to  distant  parts,  to  treat  the  alimentary  canal, 
the  urinary  or  respiratory  apparatus,  we  must  employ  soluble  or 
insoluble,  diffusible  or  non-diffusible,  liquid  or  solid,  pulverulent  or 
volatile  substances. 

The  problem  which  might  at  first  view  appear  quite  simple  is, 
therefore,  very  complex.  We  must  study  antisepsis  itself — i.  e.,  we 
must  determine  the  action  of  each  substance  upon  microbes;  then 
establish  its  toxic  equivalents  and  investigate  the  therapeutic  indica- 
tions to  which  it  may  respond. 

The  determination  of  the  antiseptic  power  of  a  substance  is  not 
as  easy  as  may  be  believed.     The  results  vary  according  to  the 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  656 

microbe  which  is  operated  upon  and  the  condition  tinder  which  we 
are  placed.  Et  is  evident  thai  the  ame  amounl  of  an  antiseptic  will 
have  different  effects  according  as  it  acts  upon  more  01  itive 

species  or  upon  cultures  provided  with  or  deprived  o  Finally, 

for  the  same  culture,  we  must  take  into  account   the  number  of 
microbes  upon  which   the  effects  of  the  antiseptic    ubstanc* 
exerted. 

In  order  to  study  the  ad  ion  of  an  antisepl  ic,  many  exj  erimei 
add  a  certain  quantity  of  i1  to  a  culture  medium,  and  then  culti 
in  the  latter  a  particular  bacterium.  Ii  is  too  often  forgotten,  how- 
ever, that,  under  these  conditions,  the  solid  or  !i<|ui<l  medium  em- 
ployed has  riot  a  fixed  constitution,  and  thai  the  results  may  vary 
from  one  day  to  another.  Ii  is,  therefore,  better  to  maki 
solutions  of  constant  composition,  for  instance,  a  mineral  solution  to 
which  a  pure  peptone  is  added.  The  medium  being  definite,  the 
addition  of  the  antiseptic  substance  may  produce  a  precipitate  which 
annihilates  the  action  of  the  germicidal  substance,  or  the  latter  may 
enter  into  a  more  or  less  stable  combination  calculated  to  diminish 
its  power  or  to  reduce  the  nutritive  property  of  the  medium.  Ii  is 
also  to  be  remembered  that  the  surrounding  temperature  exerts  an 
important  influence  upon  the  development  of  the  microbe.  At  a 
certain  degree  it  favors  its  vegetation;  as  it  advances,  however,  it 
increases  the  germicidal  action  of  the  antiseptic.  Thus,  to  cite  only 
one  example,  Chauveau  and  Arloing  have  shown  that  a  3  per  cent. 
solution  of  carbolic  acid  exerts  no  action  upon  the  bacillus  of  gaseous 
gangrene  when  its  action  lasts  for  twenty-four  hours  at  a  temperature 
of  59°  F.  (15°  C).  At  96.8°  F.  (36°  C.)  it  sterilizes  the  medium  within 
six  or  eight  hours. 

The  results  also  vary  acording  as  the  germs  operated  upon  are 
dry  or  moist.  In  the  former  case  resistance  is  much  greater.  Dr. 
Chamberland  thinks  that  the  difference  of  action  is  due  to  the  time 
necessary  to  moisten  the  dried  microbes.  In  order  to  avoid  these 
various  causes  of  error  another  method  is  frequently  resorted  to. 
Platinum  threads,  silk  threads,  pieces  of  glass,  paper,  or  linen  are 
dipped  into  the  culture  to  be  studied.  These  are  then  exposed  to 
antiseptic  vapors  or  immersed  in  the  antiseptic  fluid.  After  a  vari- 
able time  the  objects  thus  impregnated  with  cultures  are  washed 
with  sterilized  water  and  placed  in  a  nutrient  medium. 

This  method,  which  at  first  appears  as  simple  as  it  is  exact,  in 
reality  is  exposed  to  grave  errors.    In  the  first  place,  when  a  culture 


656  INFECTIOUS  DISEASES. 

is  spread  upon  any  object  whatsoever,  the  distribution  is  not  uniform. 
There  are  thicker  parts  which  do  not  undergo  the  action  of  the 
antiseptic,  except  in  their  superficial  zone.  Moreover,  in  spite  of 
prolonged  washing,  we  can  never  be  sure  of  having  removed  all  the 
antiseptic.  A  quantity  sufficient  to  prevent  multiplication  may 
remain.  Finally,  Drs.  Chamberland  and  Fernbach  have  shown  that 
the  results  vary  according  to  the  objects  used  in  the  experiments. 
Germs  spread  upon  paper  die  more  quickly  than  those  distributed 
upon  glass,  while  those  that  are  found  upon  linen  resist  for  a  still 
longer  period  of  time.  E.  Weiss  advises  addition  of  the  antiseptic 
to  a  bouillon  culture,  then  to  take  from  the  latter  a  small  drop  and 
put  it  in  a  large  amount  of  fresh  bouillon.  The  trace  of  antiseptic 
thus  introduced  is  insignificant.  This  method  is  in  fact  sufficiently 
exact  and  has  the  advantage  of  great  simplicity. 

When  the  substance  to  be  studied  is  insoluble  in  culture  media 
we  are  obliged  to  dissolve  it  previously  in  some  liquid  like  alcohol 
or  ether.  The  results  then  will  vary  according  to  the  nature  of  the 
solvent.  Finally,  when  it  is  volatile,  we  must  take  a  series  of  pre- 
cautions in  order  to  prevent  evaporation  during  the  experiment. 

These  few  considerations  show  how  complicated  the  problem 
which  is  apparently  so  simple  becomes  when  we  desire  to  study  it 
with  some  accuracy.  We  must  also  remember  that  microbes  become 
habituated  to  the  substances  that  are  harmful  to  them,  so  that  by 
making  cultures  in  series  in  media  charged  with  antiseptics  the 
multiplication  of  the  germs  becomes  progressively  easier. 

An  antiseptic  substance  produces  quite  different  effects  according 
to  the  amounts  employed.  These  effects  may  be  classified  in  the 
following  order:  In  large  doses,  sterilization,  viz.,  death  of  the  mi- 
crobes, occurs.  Next,  when  the  doses  gradually  diminish,  infertility 
of  the  medium  occurs — i.  e.,  the  microbe  remains  living,  but  it  cannot 
multiply;  when,  however,  it  is  transferred  to  another  medium,  it 
again  multiplies.  In  another  class  of  cases  the  microbe  develops,  but 
the  colonies  appear  tardily  and  are  small  in  number.  At  the  same 
time  the  functions  are  disturbed.  The  pathogenic  agents  become 
attenuated,  and  we  have  already  shown  that  the  addition  of  anti- 
septics represents  a  method  for  the  transformation  of  viruses  into 
vaccines.  At  all  events,  it  is  very  easy  to  appreciate  the  functional 
modifications  produced  by  antiseptics  in  studying  the  chromogenic 
bacteria.  Amounts  which  permit  multiplication  prevent  the  appear- 
ance of  pigment. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 


657 


finally,  there  is  a  result  analogous  to  facl   ob  erved  when  3tud 
the  action  of  poisons  upon  animals.     Anti  epticc  in  very  minute 
amounts,  far  from  hindering  the  function  of  microbe  .  stimulate  it 
to  a  notable  degree.    We  have  shown,  for  example,  thai  a  tra< 
corrosive  sublimate  favors  the  production  of  red  pigmenl   by  the 
B.  prodigiosus. 

The  experiments  performed  with  ;i  view  to  determine  the  value  of 

antiseptics  ;irc  innumerable.     In  older  to  fix  the  ideas,  il  will  suffice 

to  borrow  some  figures  from  Mequel's  scale  of  antiseptic  power.  Thb 
author  has  investigated  the  amounl  of  antiseptic  capable  of  opposing 
the  putrefaction  of  one  quart  (litre)  of  bouillon.    We  shall  mention 

only  the  substances  most  l'rc<|ucn!ly  used  in  medicine: 


Eminently  antiseptic  substance; 


Very  highly  antiseptic  substance! 


Highly  antiseptic  substances 


Moderately  antiseptic  substances 


Slightly  antiseptic  substances 


Mercury  biniodide 0  025 

Silver  iodide 0.03 

Peroxide  of  hydrogen 0  05 

Bichloride  oi  mercury    ....  0.07 

Silver  nitrate .       0.08 

I  Ismic  .'Hid  chromic  acids    ....  0  15 

Chlorine,  iodine,  cyanhydric  acid  0  _'." 

Bromi  tie,  iodoform o  80 

Bromoform 0.7 

Chloroform .        0.8 

I  lopper  sulphate 0.9 

Salicylic  ami  benzoic  acids l.o 

Picric    acid ]  .3 

Zinc  chloride [.9 

Thymic  acid 2.0 

Sulphuric,  nitric,  and  hydrochloric  acids  .       2  t«,  .', 

Carbolic  acid 3.2 

Potassium  permanganate 3.5 

Alum 4.5 

Tannin 4.8 

I    \rscnious  acid 0.0 

!  Boric  acid 7  .". 

|  Chloral  hydrate 9.3 

[Sodium  salicylate 10.0 

I  Sulphuric  ether 22.0 

j  Et  hylic  alcohol 95.0 

I  Potassium  iodide 140.0 

|  Glycerin         225.0 

[  Sodium  chlorate 400.0 


It  is  well  to  add  to  this  list  oils  the  properties  of  which  were 
already  known  to  the  ancient  world,  and  were  employed  especially 
for  purposes  of  embalming.  We  are  indebted  to  Dr.  Chamberland 
for  very  interesting  researches  on  their  antiseptic  action.  According 
to  this  scientist,  six  of  them  are  the  leading  oils.  viz..  the  essence 
of  origanum.  China  cinnamon,  Ceylon  cinnamon,  Angelica,  vespetro, 
and  geranium. 

Behring  has  studied  the  relationship  between  the  toxic  and  anti- 
septic power  of  bacillus  anthracis,  and  has  concluded  that  the  relative 
toxicity  hardly  varies.     It  oscillates  around  the  figure  6.     That  is  to 

4-2 


658  INFECTIOUS  DISEASES. 

say,  in  order  to  kill  one  kilogram  of  animal  the  substance  required 
is  six  times  smaller  than  is  required  for  sterilizing  one  quart  (1000 
cubic  centigrams)  of  liquid.  Here  are  a  few  figures  given  by  him 
and  which  may  present  a  certain  interest  from  a  practical  standpoint: 

Antiseptic  Power.     Toxic  Power.     Relative  Toxicity. 

Carbolic  acid. 1.7       gr.  0.27     gr.  6.6 

Corrosive  sublimate         .      .      .      .0.1        gr.  0.017  gr.  5.8 

Chlorohydrate  of  quinine     .       .      .    0.S       gr.  0.17     gr.  4.7 

Mercurocyanide  of  potassium  .       .    0.017  gr.  0.003  gr.  5.6 

Argent ocyanide  of  potassium    .      .    0.02     gr.  0.003  gr.  6.6 

Aurocyanide  of  potassium  .      .      .    0.04     gr.  0.006  gr.  6.6 

In  determining  the  toxic  properties  possessed  by  antiseptics  we 
must  not  be  contented  with  the  results  obtained  in  animals.  It  is 
likewise  necessary  to  remember  that  man  presents  a  peculiar  sensi- 
tiveness which  varies  from  one  subject  to  another.  All  antiseptics 
may  produce  erythemata,  a  few  may  cause  urinary  disorders,  as  is 
the  case  with  carbolic  acid,  and  lesions  in  the  mucous  membranes  of 
the  mouth  and  large  intestine,  such  as  is  the  case  with  corrosive 
sublimate.  Without  dwelling  upon  all  these  accidents,  which  are 
well  known  and  have  often  been  described,1  we  shall  cite  an  obser- 
vation which  shows  the  susceptibility  of  certain  subjects  to  antisep- 
tics. In  consequence  of  a  slight  traumatism  a  young  man  was  treated 
with  applications  of  a  mild  solution  of  corrosive  sublimate.  At  the 
end  of  fort3^-eight  hours  the  arm  was  so  red  and  swollen  that  it  was 
thought  to  be  a  case  of  erysipelas,  and  the  sufferer  was  therefore  sent 
to  our  wards.  We  there  corrected  the  diagnosis,  and,  remembering 
that  the  skin  already  irritated  by  the  application  of  some  antiseptic 
cannot  well  tolerate  the  use  of  other  substances,  we  prescribed 
simply  application  of  boiled  water.  The  symptoms  improved  quite 
rapidly.  We  then  vaccinated  the  patient,  and  before  the  inoculation, 
we  washed  the  arm  with  Van  Swieten's  solution.  On  the  following 
day  we  found  the  part  of  the  skin  which  had  come  in  contact  with 
the  mercurial  solution  red  and  swollen,  and,  what  was  altogether 
characteristic,  the  drops  of  the  solution  had  flowed  along  the  arm 
and  had  marked  their  passage  in  the  form  of  lines  of  small  pyriform 
plates  of  an  intense  red  color.  Thus,  when  an  antiseptic  is  to  be 
employed  the  choice  must  be  governed  in  view  of  the  region  to 
which  it  is  to  be  applied  and  according  to  the  effect  which  is  aimed 
at,  the  microbe  which  is  to  be  acted  upon,  and  the  special  sensi- 

1  To  see  notably  the   "  These  d'aggr6gation"  of  F.  Brun.     Des  accidents  imputables 
a.  l'emploi  chirurgical  des  antiseptiques.    Paris,  1886. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  859 

tiveness  of  the  individual,  if  this  is  known  by  hif  previou    experi- 
ence.    It  is  also  to  be  remembered  thai  it  i-  often  advantage 

to  combine  several  antiseptic  in  one  solution, for  their  i  «>'■■■  er  agaim > 
I, ho  microbes  iiici-o;isos  more  rapidly  than  i-  indicated  by  the 
total  of  the  components,  while  ju  i  the  contrary  if  true  a  regards 
thetoxicity.  II  is  well  to  recall  thai  ho1  solutioni  are  more  effective 
and  that  it  is  often  advantageous  to  add  to  the  Liquid  substances 
which  prevent  coagulation  of  the  albumins.  Lastly,  al  theend  of 
a  certain  period  of  time,  the  antiseptic  action  seeme  to  I"-  exhausted, 
and  some  other  substance  musl  then  be  employed. 

These  general  rules  will  find  their  application  in  the  rapid  review 
which  we  shall  give  of  the  antisepsis  of  various  parts  of  the  body. 
In  this  exposition  we  borrow  a  greal  number  of  documents  from 
Prof.  Bouchard's  lectures.1 

Antisepsis  of  the  Skin.  Antisepsis  of  the  skin  has  long  been 
appreciated,  and  the  ancient  lawgivers  laid  stress  upon  the  usefulness 
of  ablutions.  At  the  present  time  the  practitioner  often  utilize  anti- 
septic bathing.  He  sometimes  employs  naphthol  water  in  the  dose 
of  10  drams  for  a  bath  of  200  quarts  (40  grams  in  200  litres)  or  a 
bath  with  corrosive  sublimate  water.  The  use  of  this  last  sub- 
stance has  the  inconvenience  of  requiring  special  bath-tubs.  The 
proportion  is  2.50  to  5  drams  (10  to  20  grams)  of  corrosive 
sublimate  mixed  with  the  same  amount  of  chlorhydrate  of  ammonia. 
which  makes  a  proportion  of  0.05  to  0.1  per  thousand.  Baths 
with  corrosive  sublimate  are  daily  emploj'ed  in  our  hospitals 
for  disinfecting  the  skin  of  convalescents.  They  may  also  be  used 
in  the  course  of  certain  infections  characterized  by  cutaneous  mani- 
festations. They  are  most  frequently  used  in  the  treatment  of 
variola.  In  this  infection,  however,  we  give  preference  to  naphthol 
baths.  Naphthol  dissolved  in  alcohol  should  be  poured  into  the  bath- 
tub. A  bath  lasting  a  quarter  of  an  hour  is  given  at  the  beginning 
of  the  disease.  Secondary  infections  are  prevented  in  this  way. 
Antiseptic  bathing  is  at  present  recognized  to  be  the  best  treatment 
of  pustular  variola. 

Naphthol  baths  also  render  important  service  in  cases  of  extensive 
superficial  lesions.  The  author  employs  them  against  the  wandering 
type  of  erysipelas  as  well  as  in  furunculosis,  which  is  so  frequent  in 
consequence  of  certain  infections,  such  as  variola  and.  varicella. 

1  Bouchard.    Therapeutique  des  maladies  infectieuses.    Antisepsie,  Pari-.  1889. 


660  IXFECTIOUS  DISEASES. 

It  is  hardly  necessary  to  state  that  local  baths  may  be  prescribed 
in  cutaneous  lesions  upon  the  extremities.  This  manner  of  bathing 
gives  gratifying  results  in  the  treatment  of  panaris,  lymphangites, 
erysipelas,  and  phlegmons  on  the  limbs.  According  to  requirements, 
the  baths  are  given  with  corrosive  sublimate,  carbolic  acid,  or  potas- 
sium permanganate.  In  the  intervals  of  the  baths  compresses  dipped 
in  a  slightly  antiseptic  liquid  are  applied  to  the  affected  parts.  In 
lesions  with  gangrenous  or  putrid  tendency  the  author  uses  with 
advantage  compresses  moistened  with  peroxide  of  hydrogen.  Equal 
parts  of  commercial  peroxide  of  hydrogen  and  four  per  thousand 
sodium  bicarbonate  solution  are  mixed;  thus  the  fluid  is  neutralized, 
and  is  then  brought  to  six  volumes  by  addition  of  four  parts  of  water. 

It  should  be  remembered  that  antiseptics  are  not  always  well 
borne  by  the  skin,  that  they  often  give  rise  to  intense  and  rebellious 
dermatites,  and  that  the  local  medicinal  lesion  is  often  the  starting 
point  of  an  extensive  and  generalized  erythema.  In  such  cases  an 
application  of  another  antiseptic  only  intensifies  the  inflammation, 
and,  by  diminishing  the  resistance  of  the  skin,  favors  the  develop- 
ment of  secondary  infections.  Under  such  conditions  use  should  be 
made  simply  of  sterilized  compresses  dipped  in  boiling  water,  poul- 
tices, and  in  certain  cases,  salves  prepared  with  perfectly  neutral 
vaseline. 

Antiseptics  applied  to  the  skin  act  only  upon  the  surface.  In 
certain  cases  they  arrest  infection  of  cutaneous  glands.  Thus,  for 
instance,  applications  of  tincture  of  iodine  often  abort  the  develop- 
ment of  furuncles.  Do  they,  however,  act  as  antiseptics  or  as  stimu- 
lants? Better  results  are  obtained  simply  with  alcohol.  In  persons 
who  are  subject  to  furuncles  or  acneic  pustules  in  the  neck,  energetic 
friction  with  some  alcoholic  tincture  every  morning  is  prescribed. 
The  results  are  generally  very  good.  Alcohol  renders  valuable  service 
in  the  treatment  of  all  small  lesions  of  this  kind.  Thus  absolute 
alcohol  saturated  with  boric  acid  is  successfully  employed  against 
folliculites,  sycosis,  furuncles  of  the  auditory  canal,  etc. 

In  order  to  act  upon  the  deeper  parts  of  the  epidermis,  mechanical 
procedures,  such  as  friction  and  brushing,  may  also  be  resorted  to. 
This  is  currently  practised  in  surgery  for  disinfecting  the  field  of 
operation.  When  infection  occurs  this  procedure  is  no  longer  of  any 
use.  It  has,  therefore,  been  thought  that  the  antiseptic  would  better 
penetrate  if  thrown  in  the  form  of  jets.  Thus  carbolized  spray  is 
employed  in  anthrax,  and  corrosive  sublimate  spray  in  erysipelas. 


THEBAPEUTI08  OF  INFECTIOUS  DI8EA8E8.  661 

Antisepsis  of  the  Genital  and  Urinary  Organs.  Anti  ep  i  of  the 
genital  organs  occupied  I  lie  attention  of  ancienl  lawgivei  at  much 
as  ili;i,i,  of  i.lic  skin.  In  the  law  of  Mo  e  ,  purification  after  each 
physiological  or  pathological  flow  or  discharge  w&  pre  cribed.  Con- 
finement,  menstruation,  and  nocturnal  pollution  rendered  the  indi- 
viduals impure.  The  law  prescribed  for  the  priesl  bathing  after 
sexual  intercourse.  II  is  evidently  as  an  antiseptic  measure  thai 
certain  religions  have  ordered  circumcision. 

At  the  present-  day  it  is  customary  to  wash  the  external  genital 
organs  and  to  irrigate  the  vagina  for  purposes  of  cleanliness.  The 
rules  which  must  govern  the  disinfection  of  the  genital  organ 
almost  the  same  as  for  the  skin.  For  the  treatmenl  of  balanitis  in 
man,  injections  are  made  between  the  foreskin  and  the  glane  penis, 
but  fluids  containing  alcohol  should  be  avoided,  since  their  contad 
with  the  genital  mucous  membrane  is  very  painful.  Weak  solutions 
of  potassium  permanganate,  corrosive  sublimate,  silver  nitrate,  pro- 
targol,  or  a  20  per  1000  solution  of  liquid  subacetate  of  lead  are  used 
in  most  cases.  In  women,  under  pathological  conditions,  the  vagina 
is  disinfected  by  injection  of  the  same  substances  or  by  application 
to  the  mucous  membrane  of  gauze  or  cotton  tampons.  If  the  infec- 
tion involves  the  uterus,  antiseptics  are  more  frequently  employed. 
According  to  the  requirements  of  the  case,  the  cervix  of  the  uterus 
may  previously  be  dilated  by  means  of  a  canula,  and  lavage  given 
with  weak  antiseptic  solutions.  In  certain  instances  continuous  irri- 
gation is  resorted  to  according  to  the  method  of  Drs.  Pinard  and 
Varnier.  The  substances  most  frequently  employed  are  the  bichloride 
or  biniodide  of  mercury,  carbolic  acid,  and  permanganate  of  potassium 
in  the  proportion  of  1  :  10,000.  Mercurial  salts  often  produce  dis- 
turbances which  are  easily  overlooked  because  they  are  wrongly 
attributed  to  the  infection  which  is  being  combated.  Thus,  dysen- 
teriform  symptoms  have  sometimes  been  induced  by  mercurial 
ulceration  of  the  large  intestine. 

Antisepsis  of  the  uterus  and  bladder  may  be  practised  according 
to  two  different  procedures :  Medicinal  substances  may  be  injected 
or  ingested;  in  the  latter  case  the  medicine  reaches  the  bladder  when 
eliminated  through  the  urine.  Antisepsis  of  the  urethra  is  hardly 
ever  practised  except  in  cases  of  gonorrhea.  At  The  beginning  of  the 
infection,  the  abortive  method  may  be  resorted  to.  This  generally 
consists  in  injecting  a  1  or  2  per  cent,  solution  of  nitrate  of  silver.  In 
one-third  of  the  cases  this  method  proves  successful.     At  a  later  stage 


662  rXFECTIOUS  DISEASES. 

injections  are  used,  the  formula?  of  which  are  innumerable.  Recently, 
however,  they  have  been  replaced  by  profuse  irrigations  with  1  4000 
solution  of  potassium  permanganate.  These  irrigations  may  be 
prescribed  from  the  very  beginning  of  the  disease,  except  when  the 
infection  is  particularly  acute.  In  this  instance  the  lips  of  the  meatus 
are  swollen  and  the  canal  is  hard.  Then  the  first  treatment  must  be 
emollient.  Later  on,  when  the  acute  phenomena  have  subsided,  the 
chronic  lesions  quite  often  persist.  Gonococci  then  multiply  in  the 
prostate  gland.  Under  such  circumstances  massage  of  the  organ  is 
practised ;  fifteen  to  twenty  drops  of  a  2  per  cent,  solution  of  silver 
nitrate  or  forty  to  sixty  drops  of  a  protargol  solution  of  the  same 
strength  are  introduced.  Finally,  antisepsis  of  the  urethra  may 
likewise  be  effected  by  medicated  bougies. 

Irrigations  analogous  to  those  employed  for  the  urethra  find  appli- 
cation in  the  treatment  of  vesical  affections.  Permanganate,  pro- 
targol, or  simply  boric  acid  are  mostly  used.  These  irrigations 
act  mechanically  rather  than  chemically.  A  healthy  bladder  is  only 
exceptionally  infected.  In  the  great  majority  of  cases  cystitis 
results  from  unclean  catheterization  in  individuals  in  whom  the 
bladder  empties  itself  poorly — i.e.,  in  those  who  suffer  from  stricture 
of  the  urethra  and  particularly  from  prostatic  hypertrophy.  Stag- 
nation of  the  mine  favors  multiplication  of  the  germs.  Irrigations, 
therefore,  no  matter  what  kind,  have  the  great  advantage  of  sup- 
pressing the  principal  cause  which  induced  and  sustained  the  infec- 
tion. 

Antisepsis  of  the  urinary  passages,  ureter,  bladder,  and  urethra 
may  be  effected  by  the  administration  of  substances  which  may  be 
eliminated  by  the  kidneys.  Balsams,  such  as  copaiba,  cubebs,  santal, 
and  turpentine,  are  daily  employed  for  this  purpose.  Lastly,  salol, 
which  is  broken  up  in  the  intestine  into  carbolic  and  salicylic  acids,  is 
also  used.  Elimination  of  the  substances  through  the  urine  realizes 
a  slight  antisepsis  and  renders  valuable  service  in  the  treatment  of 
cystites. 

Antisepsis  of  the  Mouth.  Antiseptic  Treatment  of  Stomatites 
and  Anginas.  The  organs  and  cavities  of  the  face  are  easily  invaded 
by  pathogenic  germs.  Hence  the  usefulness,  even  under  normal 
conditions,  of  practising  antisepsis  of  these  parts  in  a  certain  measure. 
Greater  care  is  naturally  given  to  the  buccal  cavity. 

Even  in  health  it  is  indispensable  to  cleanse  the  mouth  and  the 
teeth  frequently.    It  is  well,  for  instance,  to  cleanse  the  teeth  in  the 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  >;<;.; 

morning,  in  the  evening,  and  after  each  meal.  Bm  he  are  gero  rally 
employed  for  this  purpose,  which  have  the  great  inconvenience  of 
retaining  organic  particles  liable  to  a  rapid  putrefaction.  Tlii  i 
remedied  by  washing  the  brush  with  some  anti  eptic  solution.  A 
good  one  is  thymic  acid  in  the  strength  of  L:3000.  In  the  <■• 
of  infectious  diseases  the  care  of  the  mouth  requires  special  attention. 
The  dryness  of  the  mucous  membrane  diminishe  it-  mean*  of  pro- 
tection and  favors  the  multiplication  of  germs  which  tend  to  invade 
the  deeper  parls  and  pcnd rate  i hrough  the  excretory  ducts,  notably 
the  parotid  gland.  1 1  will,  therefore,  be  well  to  prescribe  frequent 
lavage  with  an  alkaline  water,  viz.,  with  bicarbonate  or  borate  solu- 
tions. Antisepsis  is  not  realized  thereby,  bul  the  mucous  membrane 
is  thus  indirectly  placed  under  better  conditions  of  resistance.  I  er- 
mentation  of  carbohydrates  found  in  the  mouth  produce  acids  which 
harm  the  epithelium.  By  neutralizing  these  acids  the  alkalies  act 
in  aphtha.  While  it  is  true  that  the  fungus  producing  this  stomatitis 
lives  preferably  in  alkaline  media,  the  observation  by  Gubler  that  it 
develops  in  the  mouth  when  the  medium  becomes  arid  and  ci 
to  multiply  when  the  latter  is  rendered  alkaline,  is  simply  due  to  the 
fact  that  acids  diminish  the  vitality  of  the  mucous  membrane,  and 
not,  as  has  long  been  asserted,  because  they  favor  the  vegetation  of 
the  fungus. 

When  infection  is  more  profound,  profuse  lavage  of  the  mouth  is 
generally  practised.  The  patient  sits  up,  inclines  the  head  forward 
while  the  antiseptic  fluid  is  thrown  into  the  mouth.  A  good  many 
mixtures  have  been  proposed.  In  our  wards  we  employ  in  stomatites 
and  anginas  a  solution  containing  10  per  1000  of  carbolic  acid  and 
1  per  1000  of  thymol.  Solutions  of  chloral  hydrate.  1: 100.  are  also 
very  good.  When  microbic  lesions  are  already  developed  applica- 
tions of  antiseptic  or  caustic  substances  should  be  made.  In  stoma- 
tites, whatever  their  nature  may  be,  cauterizations  by  alum,  nitrate 
of  silver,  and  especially  salicylic  acid,  are  practised,  the  latter  being 
used  in  the  proportion  of  1 :  10  dissolved  in  a  mixture  of  equal  parts 
of  alcohol  and  glycerin.  Phenol,  or  sulphorieinated1  salol  or  tincture 
of  iodine  are  also  useful.  We  have  often  obtained  satisfactory  results 
from  the  employment  of  tincture  of  cochlearia. 

There  is  a  special  form  of  gingivitis — expulsive  gingivitis— which 

1  There  is  a  French  preparation,  "acide  sulforicinique,"  composed  of  oleum  ricini  and 
sulphuric  acid.  Antiseptic  substances,  such  as  salol  and  phenol,  may  be  combined 
with  this  acid  to  form  sulphorieinated  salol.  or  phenol,  etc. — Translator. 


664  INFECTIOUS  DISEASES. 

is  very  grave  because  it  causes  shedding  of  the  healthy  teeth.  It 
should  be  treated  by  strong  antiseptics,  such  as  carbolic,  salicylic, 
or  chromic  acid.  Finally,  such  antiseptics  as  creosote,  methyl  sali- 
cylate, and  arsenious  acid  are  employed  for  the  treatment  of  dental 
caries. 

In  most  cases  of  anginas  antiseptic  lavage  is  sufficient.  In  per- 
sistent lesions,  however,  painting  with  more  energetic  antiseptics  is 
indicated.  Tincture  of  iodine,  salol,  hydroglycerinated  solutions  of 
corrosive  sublimate,  and  camphorated  naphthol  are  the  substances 
most  frequently  employed.  It  is  well,  however,  not  to  prolong  their 
use,  since  they  produce  irritation  and  maintain  the  lesion  against 
which  they  are  directed.  The  therapeutic  indications  are  the  same 
in  suppurating  tonsillites.  Gargles  or,  still  better,  slightly  antiseptic 
lavage,  is  also  prescribed.  In  some  cases  puncture  of  the  abscess  is 
at  a  certain  moment  to  be  practised.  An  emetic  is  sometimes  admin- 
istered for  this  purpose,  but  this  medication  acts  only  when  the  lesion 
is  at  the  point  of  opening  spontaneously.  It  is  then  useless  and,  what 
constitutes  a  graver  objection,  it  has  the  inconvenience  of  depressing 
the  patient. 

Unlike  the  buccal  cavity,  the  nasal  cavity  does  not  need  antiseptic 
lavage  in  health.  In  the  course  of  infectious  diseases  it  is  well  to 
introduce  a  slightly  volatile  antiseptic  substance.  Mentholated  olive 
oil  in  the  proportion  of  1 :  40  fulfils  this  indication ;  every  morning 
five  or  six  drops  of  it  are  introduced  into  the  nostrils.  A  salve  con- 
taining twenty  grams  of  vaseline,  one  gram  of  resorcin,  and  half  a 
gram  of  menthol  is  also  employed.  When  the  nasal  fossa?  are  more 
particularly  affected,  whether  the  lesion  be  primary  or  secondary, 
antisepsis  is  likewise  indicated. 

Simple  corj^za  is  often  cured  when  slightly  antiseptic  powders  are 
employed  from  the  beginning.  Many  formulas  have  been  given.  The 
author  generally  employs  a  mixture  made  with  equal  parts  of  pul- 
verized boric  acid,  benzoin  powder,  and  salicylate  of  bismuth.  Ten 
grams  of  each  of  these  substances  are  prescribed,  and  a  half  gram 
of  hydrochlorate  of  cocaine  is  added. 

Serious  rhinites  are  sometimes  observed  in  the  course  of  certain 
infections.  The  purulent  rhinitis  of  scarlatina  represents  a  very 
important  cause  of  death.  Its  treatment  must  be  energetic.  We 
have  recourse  to  lavage  with  peroxide  of  hydrogen.  In  order,  how- 
ever, to  insure  cleansing  of  the  nasal  fossse,  flow  of  the  discharge  from 
within  outward  must  be  secured.    Inflammation  of  the  nasal  fossae 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  666 

may  spread  it  to  the  sinuses  of  the  face.  This  complication  i 
readily  be  recognized  by  the  following  two  symptoms:  n  purulent 
discharge  from  one  nostril  and  a  facial  neuralgia.  The  treatment 
consists  in  causing  the  patient  to  inhale  through  the  di  eased  nostril 
by  means  of  a  funnel  turned  upside  down  upon  a  bowl  of  hoi  water 
intowliic.h  has  been  poured  a  teaspoonful  of  a  4  per  cent,  alcoholic 
solution  of  menthol.  The  inhalations  are  repented  hourly;  each 
sitting  should  Last  five  minutes.  II'  the  inflammation  involves  the 
Eustachian  tube  and  the  middle  ear  this  new  complication  Bhould  be 
combated  by  paracentesis  of  I  lie  tympanum  and  irrigation.  In  our 
wards  we  employ  lavage  with  bonded  water,  which  is  followed  by 
the  introduction  of  a  few  drops  of  carbolized  glycerin.  We  have 
recently  obtained  highly  satisfactory  results  from  lavage  with  a 
1:500  solution  of  methylene  blue. 

Finally,  in  order  to  conclude  what  we  have  to  say  about  antisep- 
sis of  the  face,  we  shall  recall  what  care  is  to  be  given  to  the  ocular 
apparatus.  Conjunct  ivites  are  frequent  in  infections;  they  are, 
however,  generally  benign.  They  heal  under  use  of  simple  washings 
with  hot  borated  water,  followed  by  an  occlusive  dressing.  In  case 
of  severe  pain,  a  drop  of  a  collyrium  made  with  neutral  sulphate 
of  atropine  is  instilled  into  the  eye. 

Three  infections  frequently  give  rise  to  grave  lesions  of  the  eyes. 
These  are  zona,  variola,  and  gonorrhea.  In  the  case  of  zona,  atropine 
and  absolute  occlusion  of  the  eye  are  prescribed.  Variola  often  pro- 
duces purulent  conjunctivites,  the  principal  danger  of  which  is  con- 
secutive keratitis.  For  conjunctivitis  we  employ  lavage  with  1 :  8000 
solution  of  potassium  permanganate,  5:1000  solution  of  protargol, 
or  1:500  solution  of  methylene  blue.  Should  keratitis  supervene, 
methylene  blue  alone  is  applicable.  At  the  same  time  atropine  is 
utilized  to  some  extent. 

The  treatment  of  purulent  gonorrheal  conjunctivitis  consists  in 
applications  of  silver  nitrate  or  protargol. 

Antisepsis  of  the  Respiratory  Passages.  Antisepsis  of  the  re- 
spiratory passages  may  be  realized:  (1)  by  inhalations  of  volatile 
substances;  (2)  by  directly  introducing  liquids  or  powders  into  the 
upper  parts  or,  in  the  case  of  the  lungs,  by  injecting  them  directly 
into  their  parenchyma;  (3)  by  turning  to  profit  elimination  through 
the  alveoli  of  certain  volatile  principles  which  may  be  introduced 
into  the  organism  by  any  channel. 

Inhalations  of  volatile  substances  are  daily  employed  in  the  treat- 


(366  ISFECTIOUS  DISEASES. 

ment  of  laryngeal,  tracheal,  or  bronchial  infections.  Menthol  is 
commonly  used.  A  4  per  cent,  alcoholic  solution  is  made  use  of.  A 
dessertspoonful  of  this  is  put  in  a  bowl  of  hot  water  and  the  latter 
covered  with  an  inverted  funnel,  and  inspiration  made  through  the 
tubal  part  of  the  funnel.  Another  method  consists  in  causing  the 
patient  to  breathe  an  atmosphere  charged  with  medicated  vapors. 
Tar  is  often  employed  for  this  purpose.  Dr.  Tapret  has  proposed  to 
have  patients,  particularly  tubercular  subjects,  sojourn  in  rooms  in 
which  a  10  per  1000  creosote  solution  is  sprayed.  We  may  also  men- 
tion sulphurous  waters,  which  are  employed  in  chronic  infections. 
In  other  instances  water  charged  with  antiseptic  substances  is 
sprayed  in  front  of  the  mouth  of  the  sufferer.  Naphtholated  water 
(naphthol  0.25,  alcohol  25  grams,  water  75  grams),  Van  Swie ten's 
solution,  1 :  1000  solution  of  biniodicle  of  mercury,  carbolized  water, 
and  water  charged  with  oil  of  turpentine  or  creosote  have  also  been 
utilized. 

The  respiratory  tract  being  largely  open  to  the  exterior,  medicines 
may  easily  be  introduced  therein.  This  is  currently  done  as  regards 
the  larynx.  Antisepsis  is  thus  realized  just  as  in  the  case  of  a  surface 
exposed  to  the  air.  As  regards  the  more  deeply  seated  parts,  we 
have  to  be  contented  with  injecting  a  few  drops  through  the  larynx 
or,  in  the  case  of  tracheotomy,  through  the  tracheal  wound.  Men- 
tholated oil  in  the  proportion  of  1  :  40  is  generally  employed. 
Should  it  be  thought  advantageous,  injections  by  means  of  a  needle 
introduced  through  the  skin  into  the  trachea  may  readily  be  prac- 
tised. 

In  the  presence  of  a  well-circumscribed  pulmonary  focus  one  is 
always  tempted  to  inject  some  antiseptic  directly  into  it.  Numerous 
experiments  have  been  made  in  this  direction,  notably  by  Dr.  Lepine 
and  Dr.  True.  It  is  necessary  not  to  exceed  1  c.cm.  or  2  c.cm.  beyond 
the  surface  of  the  lung,  in  order  to  avoid  entering  an  important 
vessel.  By  injecting  the  fluid  slowly  it  is  possible  to  introduce  a 
considerable  amount  of  it.  Lepine  injected  as  much  as  100  c.cm. 
through  five  different  punctures.  Benzoate  of  soda  and  potassium 
iodide  have  been  introduced  in  this  manner.  Lepine  utilized  bin- 
iodide  of  mercury  in  a  dose  of  1 :  40,000.  These  attempts  have  been 
made  particularly  in  pneumonia.  It  would  be  interesting,  however,  to 
renew  these  attempts  in  cases  of  circumscribed  pulmonary  gangrene. 

The  majority  of  volatile  substances  that  are  eliminated  through 
the  respiratory  apparatus  may  exercise  a  medicinal  action  while 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8ES.  667 

being  eliminated,  no  matter  through  which  channel  they  are  intro- 
duced. According  i,o  this  principle,  if  i  rational  to  cause  patienfa 
to  ingest  preparations  of  turpentine  or  eucalypti!  .  potion  containing 
from  four  to  six  grams  of  hyposulphite  of  soda,  or  to  administer  for 
the  same  purpose  sulphurous  waters.  According  to  the  same  idea, 
the  use  of  gaseous  enema  I  a,  of  carbonic  add,  and  sulphuretted  hydro- 
gen has  been  advised.  Too  much  reliance,  however,  should  nol  be 
placed  upon  this  method,  since  we  have  recognized,  with  Dr.  Gamier, 
that  sulphuretted  hydrogen,  even  when  introduced  in  large  amounts, 
is  not  found  in  flie  exhaled  air.  At  least  il  ii  impo  ible  to  detect 
the  slightest  trace  of  it  by  placing  before  the  mouth  of  the  patienl 
a  paper  preparation  of  acetate  of  lead. 

For  the  treatment  of  respiratory  affections  the  subcutaneous 
method  may  likewse  be  utilized.  Eucalyptol  is  often  injected  in 
this  manner.  Creosote  is  also  administered  either  per  os,  or  by  sub- 
cutaneous injections,  or  through  enemata.  In  the  first  case,  pills  of 
10  centigrams  are  generally  employed,  of  which  three  to  five  are 
taken  with  the  two  principal  meals.  In  the  second  case,  oily  solu- 
tions in  the  proportion  of  1  :  15  are  used.  Burlureaux  advia 
inject  them  slowly  at  the  rate  of  forty  drops  per  minute,  which  means 
20  grams  in  an  hour.  As  much  as  100  grams  and  even  150 
grams  of  the  fluid  have  been  introduced  in  this  manner.  In  general 
it  is  convenient  to  prescribe  an  enema  containing  from  4-  gram  to 
1  gram  of  creosote  incorporated  in  an  oily  emulsion.  The  skin  may 
often  be  painted  with  creosote  or  guaiacol.  Such  applications  are 
well  borne  when  they  are  not  too  strong.  They  have  the  strange 
property  of  lowering  the  temperature  and  producing  alarming  mani- 
festations if  the  dose  of  creosote  is  too  large.  The  author  prescribes 
friction  with  a  10  per  cent,  guaiacolated  salve  the  size  of  a  hazel- 
nut. In  fact,  the  recent  tendency  is  to  substitute  for  creosote  some 
well-defined  chemical  product,  such  as  guaiacol,  or  less  irritating 
substances,  such  as  carbonate  of  creosote  or  of  guaiacol.  Creosote  and 
its  derivatives  render  service  in  the  treatment  of  all  torpid  infections 
of  the  respiratory  passages,  particularly  in  cases  of  tuberculosis. 
They  are  not  without  some  disadvantages.  Creosote  sometimes  pro- 
duces digestive  disturbances  which  are  avoided  by  administering  it 
in  the  form  of  enemas.  Some  authorities  believe  that  it  produces 
congestion  and  hemoptysis.  Therefore,  its  administration  is  to  be 
avoided  in  those  cases  of  tuberculosis  in  which  there  is  tendency  to 
pulmonary  hemorrhages.    Contrary  to  what  has  been  stated  by  some. 


6S8  INFECTIOUS  DISEASES. 

creosote  is  often  useful  in  acute  forms,  and  it  is  still  the  best  medicine 
for  the  treatment  of  chronic  pulmonary  tuberculosis. 

Antisepsis  of  the  Alimentary  Canal.  The  intensity  of  putrefac- 
tions that  occur  even  normally  in  the  digestive  canal,  the  frequency 
and  gravity  of  disturbances  resulting  therefrom,  the  role  of  gastro- 
intestinal putrefactions  in  the  development  of  infectious  or  non- 
infectious secondary  lesions,  having,  apparently,  nothing  to  do  with 
digestive  disorders,  explain  why  therapeutists  have  multiplied  their 
efforts  to  combat  the  microbes  which  swarm  in  this  part  of  the 
organism.  Three  principal  methods  are  now  at  our  disposal.  We 
may  restrain  fermentations  by  suppressing  fermentable  aliments. 
We  may  expel  the  infected  remains  of  digestion  and  at  the  same 
time  sweep  off  microbes  and  their  toxins.  Finally,  we  may  prescribe 
antiseptic  substances. 

The  digestive  canal  may  be  rendered  antiseptic  by  means  of  diet. 
For  the  adult,  milk  diet  is  generally  prescribed,  the  influence  of 
which  in  this  regard  was  clearly  demonstrated  by  the  investigations 
of  Gilbert.  In  mild  cases  it  suffices  to  modify  the  diet  and  restrict 
readily  putrescible  foods  like  meat.  On  the  other  hand,  rice,  vege- 
tables, and  cooked  foods  are  prescribed.  In  a  grave  case,  even  milk 
is  too  fermentable.  All  alimentation  is  to  be  suppressed  and  the 
patient  placed  on  water  diet.  This  is  particularly  indicated  in  the 
case  of  the  newborn  suffering  from  gastrointestinal  disturbances 
which  at  times  rapidly  prove  fatal.  Boiled  water  to  which  is  added 
a  small  amount  of  sugar  and  10:1000  of  lactic  acid  is  given.  As 
ill-digested  aliments  are  easily  attacked  by  microbes,  gastrointestinal 
antisepsis  can  likewise  be  effected,  although  in  an  indirect  manner, 
by  modifications  of  alimentary  hygiene.  It  is  probable  that  the 
ingestion  of  hydrochloric  acid  acts  in  this  manner.  This  acid  was 
considered  as  an  antiseptic  secreted  by  the  mucous  membrane  of  the 
stomach.  The  intense  fermentations  of  hyperchlorhydria  are  due  to 
the  fact  that  the  food  is  not  well  digested.  Alkalies  will  then  diminish 
putrefactions  and,  reciprocally,  hydrochloric  acid  will  play  the  same 
role  in  cases  of  hypochlorhydria. 

Microbes  may  be  mechanically  thrown  out.  Profuse  lavage  of  the 
stomach  or  intestine  possesses  the  treble  advantage  of  freeing  the 
digestive  canal  of  fermentable  substances,  microbes,  and  toxic  prod- 
ucts resulting  from  their  multiplication.  The  same  indication  is 
fulfilled  by  the  use  of  emetics  and  purgatives.  The  secretions  and 
fluxes  provoked  by  them  bring  about  a  similar  cleansing.     Among 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  869 

purgatives  calomel  seems  to  be,  in  thi    respect,  the  most  efficient, 
for  Lt  exerts  at  the  same  time  an  antiseptic  action. 

(j!;i,si,r()iiii,<\s!Jii:il  antiseptics,  properly  so  called,  may  be  divided 
from  a  practical  standpoint  into  two  groups:   soluble  and  insoluble 
antiseptics.   The  soluble  ones  most  frequently  employed  are  sulpho- 
earbonafed  wafer,  diloroform  water,  and  solutions  of  lactic  and  car- 
bolic acid.    It  has  been  noted,  however,  thai  these  substanct 
they  advance  in  the  alimentary  canal  are  absorbed  and  booh  disap- 
pear.   Therefore,  their  germicidal  influence  n  exerted  upon  a 
limited  extent  of  flic  digestive  tract.    Hence,  it  hae  been  recom- 
mended to  prescribe  insoluble  antiseptics,  pari  of  which  may  be 
modified  and  penetrate   flic   organism,   while  another   part    pi 
through  the  whole  length  of  the  canal  withoul  any  alteration. 

Naphtholin  was  first  praised.  It  has,  however,  been  abandoned, 
for  it  often  produces  dysuria  and  pruritus,  and  may  be  dangerous  to 
the  sight,  judging  from  the  cataract  which  is  caused  by  its  ingestion 
in  rabbits.  In  consequence  of  Prof.  Bouchard's  experiments,  ,i- 
naphthol  was  utilized, instead  of  which,  according  toDr.Maximowieh, 
a-naphthol  may  be  used,  which  has  the  double  advantage  of  being 
more  antiseptic  and  less  toxic.  The  burning  taste  of  naphthol  makes 
it  necessary  to  administer  it  in  wafers.  It  may  be  given  alone  or 
associated  with  laxative  or  antidiarrheal  substances.  The  dose  is 
from  one  to  three  grams  in  twenty-four  hours.  It  is  well,  however, 
to  administer  it  in  fractional  doses,  since  the  successive  use  of  small 
doses  produces  a  more  marked  antiseptic  action  than  the  same 
amount  ingested  at  once,  and  is  less  irritating  for  the  stomach.  In 
order  to  avoid  the  inconveniences  due  to  the  caustic  property  of 
naphthol,  two  of  the  derivatives  of  this  medicine,  betol  and  benzo- 
naphthol,  are  at  present  frequently  made  use  of.  Their  antiseptic 
power  is  not  as  great,  but  they  are  well  borne  even  by  delicate 
stomachs,  while  naphthol  itself  has  the  inconvenience  of  causing  pain 
and  gastric  burning  in  certain  individuals.  Benzonaphthol,  which  is 
the  one  commonly  employed,  is  prescribed  in  daily  doses  of  from  two 
to  four  grams.  It  is  tasteless  and,  therefore,  can  be  given  to  children 
and  such  patients  whose  prostrated  condition  prevents  them  from 
swallowing  wafers.  It  may  be  administered  in  wafers,  powders,  in 
which  case  it  is  taken  in  some  liquid,  and  finally,  in  the  form  of  a 
potion. 

Iodoform,  which  has  sometimes  been  employed  as  an  intestinal 
antiseptic,  is  hardly  ever  used  now  for  this  purpose.    Salol,  in  doses 


6  70  IXFECTIO  US  DISEA  SES. 

of  from  2  to  4  grams,  acts  particularly  upon  the  stomach;  in 
fact,  it  is  decomposed  in  the  duodenum  into  carbolic  and  salicylic 
acids,  which  are  soon  absorbed.  This  medicine  is  especially  useful 
when  there  is  reason  to  believe  that  infection  has  invaded  the  biliary 
passages,  salicylic  acid  passing  into  the  bile,  where  its  aseptic  action 
is  exerted. 

Subnitrate  or  salicylate  of  bismuth  is  often  combined  with  the 
antiseptics  above  indicated.  Salicylate  of  bismuth  is  decomposed  in 
the  presence  of  sulphuretted  hydrogen  originating  from  intestinal 
putrefaction;  insoluble  bismuth  sulphide  is  produced,  and  the  salicylic 
acid  thus  liberated  is  found  in  the  urine,  in  which  it  may  be  detected 
by  means  of  perchloride  of  iron.  Some  authors  believe  that  this 
offers  a  very  simple  means  of  determining  the  intensity  of  digestive 
putrefactions.  Instead  of  administering  through  the  mouth,  anti- 
septics may  be  introduced  by  the  rectum.  Various  medicinal  enemas 
have  been  favored.  Those  with  carbolic  acid  were  once  quite  fre- 
quently employed. 

Although  enemas  are  of  service,  they  have  the  inconvenience  of 
affecting  only  the  terminal  part  of  the  large  intestine.  On  the  other 
hand,  the  fluid  arriving  under  a  certain  pressure  distends  the  rectal 
enlargement,  and  thus  aggravates  or  maintains  certain  disorders. 
Irrigation  by  means  of  a  soft  sound  introduced  into  the  colon  is  free 
from  this  disadvantage.  Very  slight  pressure  may  be  employed,  so 
that  the  liquid  flows  slowly  and,  being  introduced  deeply  into  the 
canal,  cleansing  is  more  complete.  Another  advantage  of  this  method 
is  that  a  large  amount  of  fluid  may  be  circulated.  Mild  solutions  of 
potassium  permanganate  are  often  used  (1 :  10,000)  and  give  very 
satisfactory  results  in  the  treatment  of  dysentery  and  dysenteriform 
ententes.  Cantani  employed  in  cholera  a  fluid  containing  from  3  to 
6  grams  of  tannin,  30  to  50  grams  of  gum  arabic,  and  30  to  50  drops 
of  laudanum  per  litre  (quart).  Of  course,  the  formulas  may  be 
varied  ad  infinitum.  We  shall  first  notice  the  advantages  obtained 
from  intestinal  lavage  with  subnitrate  of  bismuth.  This  substance, 
being  deposited  upon  the  mucous  membrane,  forms  a  protective  layer, 
and  may  keep  the  antiseptic  incorporated  in  contact  with  the  diseased 
parts.  In  order  to  introduce  bismuth,  which  is  given  in  doses  of  from 
10  to  20  grams,  it  is  suspended  in  quince  mucilage  or  gum  arabic 
water. 

In  cases  of  infection  of  the  large  intestine  we  have  obtained  remark- 
able results  from  the  use  of  lavage  with  peroxide  of  hydrogen.    We 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8E8.  07] 

introduce  from  .r)0  c.cm.  to  LOO  c.cm.  of  peroxide  of  hydrogen,  which 
is  rendered  alkaline  just  before  use  by  the  addition  of  a  double  volume 
of  Vichy  water.  Peroxide  of  hydrogen  may  al  o  be  poured  into  a 
litre  (quart)  of  boiling  water  in  which  should  be  dissolved  5  grams 
of  sodium  chloride,  :;  grams  of  sodium  pho  phate,  and  \  gram  of 
sodium  bicarbonate.  Peroxide  of  hydrogen  acta  a  an  antiseptic. 
'The  oxygen  which  is  Liberated  hinders  the  development  of  the  numer- 
ous anaerobic  microbes  inhabiting  the  intestine  and  al  the  same 
time  exercises  ;i  very  f;ivor;il)le  stimulation  upon  the  walk  of  the 
digestive  canal.  This  medication  is  particularly  useful  in  the  treat- 
ment of  oolites  ;i,ik|  notably  dyscuteriform  COlite  , 

Digestive  antisepsis  is  evidently  indicated  in  gastrointestinal  in- 
fections. An  attack  of  indigestion,  seasonal  diarrheas,  alimentary 
poisonings,  as  well  as  typhoid  fever,  cholera,  and  dysentery,  are  well 
treated  by  this  medication.  In  typhoid  fever  the  administration  of 
naphthol  or  benzonaphthol  lias  the  advantage  of  diminishing  toxic 
manifestations  by  checking  putrefactions.  The  tongue  remains 
moist,  delirium  is  rare,  tympanites  less  marked,  and  the  i'ccul  matters 
are  almost  odorless.  As  gastrointestinal  putrefactions  play  a  con- 
siderable role  in  a  number  of  infectious  diseases,  the  use  of  am  i>ej  >t  ics 
is  frequently  indicated.  In  affections  of  the  liver  and  kidneys,  the 
transformation  and  elimination  of  the  intestinal  poisons  being  imper- 
fectly effected,  it  is  important  to  diminish  this  principal  source  of 
intoxication.  The  same  is  true  of  certain  cutaneous  infections. 
Prof.  Bouchard  long  ago  laid  stress  upon  the  excellent  efTec*  - 
intestinal  antisepsis  in  combating  acne  and  furunculosis.  Beer  yeast 
probably  acts  in  an  analogous  manner  by  regulating  the  digestive 
functions. 

Antisepsis  of  the  Serous  Membranes.  Antiseptics,  once  fre- 
quently employed  against  infections  of  serous  membranes,  are  no 
longer  used,  except  in  accordance  with  certain  indications.  The 
physician  is  guided  bj7-  the  course  or  the  bacteriological  nature  of  the 
effusion.  Thus,  in  pleurisies  with  the  pneumococcus,  one  or  several 
thoracenteses  often  suffices.  In  streptococcic  or  in  pneumococcic 
pleurisies,  which  are  reproduced  repeatedly  or  are  developed  within 
a  partition  of  the  pleura,  operation  for  empyema  with  or  without 
costal  resection  is  resorted  to.  After  the  focus  is  opened  it  is  well 
to  irrigate  with  a  mild  antiseptic  solution,  for  example,  a  1 :  1000 
solution  of  corrosive  sublimate.  The  cavity  is  Then  washed  out  with 
boiled  water  in  order  to  carry  away  the  antiseptic.    In  the  majority 


672  INFECTIO  US  DISEASES. 

of  cases  a  single  lavage  suffices.  If,  however,  the  fluid  is  rapidly 
reproduced,  or  it  becomes  fetid,  or  the  patient  presents  symptoms 
due  to  purulent  absorption,  antiseptic  lavage  should  again  be  resorted 
to.  For  the  same  reason  these  irrigations  should  always  be  employed 
in  cases  of  putrid  pleurisies.  If  the  effects  of  corrosive  sublimate  are 
feared  a  4  per  cent,  solution  of  creolin,  a  1  per  cent,  solution  of 
chloride  of  zinc,  or  1  or  2  per  cent,  solution  of  salicylic  acid  may 
be  used.  Not  infrequently,  however,  the  practitioner  substituting 
asepsis  for  antisepsis  is  contented  with  lavage  with  boiled  water. 

In  cases  of  purulent  tubercular  pleurisy  surgical  intervention  does 
not  yield  very  successful  results.  It  has,  therefore,  been  suggested 
to  inject  antiseptic  solutions  into  the  pleura.  Camphorated  naphthol 
particularly  has  been  used  in  this  case. 

Interstitial  Antisepsis.  Interstitial  antisepsis  may  be  practised 
by  introducing  germicidal  fluids  into  the  diseased  tissues.  The 
remarkable  results  obtained  by  this  method  in  the  treatment  of 
malignant  pustule  are  well  known.  Davaine  and  Cezard  were  the 
first  to  treat  anthrax  infection  by  means  of  interstitial  injections  of 
iodine.  They  began  with  1:  4000  solutions  and  gradually  increased 
to  1  :  400  dilutions.  Far  more  concentrated  solutions  may  easily 
be  employed.  The  author  recommends  a  mixture  of  one  part  of 
tincture  of  iodine  with  one  or  two  parts  of  iodided  water.  Fifteen 
to  20  drops  of  this  liquid  are  injected  into  the  swollen  parts  every 
morning  and  evening  by  three  or  four  punctures  made  around  and 
outside  the  vesicular  zone.  The  needle  is  obliquely  introduced  be- 
neath the  skin  and  the  fluid  is  injected  very  slowly.  The  author  also 
makes  subcutaneous  injections  around  the  congested  glands.  The 
treatment  is  thus  continued  every  day  by  regulating  the  amount  of 
the  fluid  to  be  introduced  according  to  the  general  state  of  the  patient 
and  the  aspect  of  the  local  lesion.  The  injections  should  not  be 
suspended  until  amelioration  is  well  marked,  edema  is  diminished, 
the  skin  recovers  its  suppleness,  and  fever  has  disappeared.  During 
and  after  employment  of  iodine  injections  it  is  well  to  keep  the 
pustule  covered  with  an  antiseptic  dressing,  such  as  Van  Swieten's 
solution,  mercurial  ointment  (Cucco),  camphorated  naphthol,  etc. 
When  the  eschar  separates  the  part  is  covered  with  iodoform.  Thus 
the  too  rapid  development  of  pyogenic  agents  and  other  accidents 
may  be  avoided. 

Subcutaneous  injections  of  tincture  of  iodine  are  well  borne, 
although  they  are  somewhat  painful.    Some  transitory  phenomena  of 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8E8.  i;7 .; 

iodism  may  at  times  occur  under  their  influence.  In  om 
observed  at  the  point  of  several  punctures  little  painful  indurations 
which  finally  healed  at  the  end  of  a  few  weeks  without  any  accident. 
Russian  surgeons  have  employed  for  the  same  purpo  e  a  olution  of 
corrosive  sublimate.  Good  results  have  also  been  obtained  with  \\ 
per  cent,  .solutions  of  carbolic  acid.  This  fluid  is  well  borne  and 
gives  rise  lo  no  disturbance. 

II,  has  been  suggested  to  treal  erysipelas  in  the  same  manner  and, 
in  order  to  arrest  its  spread,  in  inject  antiseptic  fluids  a1  the  margin 
of  the  inflamed  part.  In  the  case  of  facial  erysipelas,  however,  the 
evolution  seems  to  us  too  favorable  to  necessitate  so  delicate  a 
method.  In  erysipelas  of  the  limbs,  and  especially  of  the  l< 
extremities,  with  tendency  to  diffuse  suppuration  and  sphacelus,  the 
author  has  several  times  injected  peroxide  of  hydrogen.  He  has 
always  utilized  the  commercial  solution  diluted  with  an  equal  volume 
of  a  4  :  1000  sodium  bicarbonate  solution.  The  fluid  thus  obtained 
is  injected  beneath  the  skin  through  several  punctures  in  such  a 
manner  as  to  surround  the  lesion.  From  5  to  10  c.cm.  of  the  fluid 
is  thus  introduced  morning  and  evening.  These  injection-  produce 
truly  marvellous  effects,  and  in  several  cases  they  have  speedily 
arrested  the  invading  course  of  a  suppurated  or  gangrenous  Lesion. 

When  a  part  is  attacked  by  sphacelation  and  seems  irretrievably 
lost,  an  attempt  may  be  made  to  transform  it  into  a  harmless  mass 
by  a  sort  of  embalmment.  This  is  what  Prof.  Bouchard  realized  in  a 
case  of  gangrene  of  the  lower  extremity  due  to  post-typhoidal  arter- 
itis. He  prescribed  injections  of  a  25  per  cent,  creosote  solution  into 
the  diseased  limb.  The  putrefaction  was  rapidly  arrested:  the  gan- 
grenous member  became  mummified,  and  was  subsequently  elimin- 
ated by  spontaneous  amputation. 

General  Antisepsis.  A  last  question  remains:  Is  general,  at  least 
relative,  antisepsis  possible?  Is  it  possible  to  diminish,  if  not  to 
abolish,  the  aptitude  of  the  fluids  and  tissues  to  microbic  invasions  ? 

It  is  certain  that  we  here  encounter  great  difficulties  and  that 
antiseptic  substances  are  too  toxic  to  be  administered  in  amounts 
responding  to  this  end.  In  two  instances  the  experiment  was  made 
involuntarily :  It  occurred  at  the  time  when  carbolized  enemas  were 
administered  in  the  treatment  of  typhoid  fever.  Inadvertently  the 
mother  solution  was  injected  into  two  patients.  Fearful  manifesta- 
tions immediately  occurred,  but  profuse  intestinal  irrigation  prac- 
tised forthwith  succeeded  in  carrying  out  the  poison.     The  curious 

43 


674  INFECTIOUS  DISEASES. 

fact,  however,  is  that  the  fever  fell  and  did  not  rise  again.     The 
disease  was  checked,  but  the  fatal  dose  had  nearly  been  reached. 

There  is,  however,  an  inoffensive  substance  which,  according 
to  some  scientists,  renders  the  organism  aseptic.  This  substance 
is  tannin.  The  simple  injection  of  this  medicine,  it  is  said,  suf- 
fices to  render  the  blood  unfavorable  for  the  development  of  mi- 
crobes. It  is  evidently  interesting  to  resume  the  study  of  these 
phenomena. 

While  it  is  hardly  possible  to  realize  general  antisepsis  of  the 
organism  against  the  majority  of  microbes,  we  are  able,  by  the  use 
of  specifics,  to  prevent  the  development  of  certain  determined 
agents.  The  medicines  described  under  this  name,  at  least  some  of 
them,  hinder  the  multiplication  of  a  given  microbe.  These  are  selec- 
tive antiseptics.  At  least  this  has  been  demonstrated  for  the  salts 
of  quinine  in  paludism.  The  germicidal  serums  act  in  the  same 
manner,  and  the  facts  already  known  lead  us  to  the  hope  that  we 
shall  see  an  increase  in  the  list  of  substances  to  which  certain  microbes 
are  so  sensitive  that  minute  amounts,  in  nowise  dangerous  for  the 
organism,  suffice  to  arrest  their  development. 

Conclusion.  If  we  consider  the  present  tendency  of  surgeons  we 
find  that,  after  having  used  and  at  times  abused  antiseptics,  there 
is  a  growing  inclination  to  more  and  more  restrict  their  employ- 
ment. 

Strong  antiseptics  are  rejected  and  reserved  for  certain  exceptional 
cases.  On  the  other  hand,  asepsis  is  often  substituted  for  antisepsis 
by  the  use  of  lavage  with  boiled  water.  When  antiseptics  are  em- 
ployed, all  those  which  may  produce  a  caustic  action  should  be 
eliminated,  and  it  should  be  borne  in  mind  that  germs  seem  to  become 
rapidly  habituated  to  their  germicidal  action.  It  is,  therefore,  neces- 
sary to  frequently  change  the  substances  employed.  Moreover,  it  is 
well  to  remember  that  an  antiseptic  often  acts  as  much  by  stimu- 
lating the  tissues  as  by  destroying  the  microbes.  The  latter  are  well 
protected  within  the  organism.  They  seldom  vegetate  upon  the  sur- 
face. They  penetrate  into  the  folds  of  the  tissues  and  especially  into 
the  glandular  crypts,  vegetate  behind  masses  of  cells,  and  are  thus 
protected  against  antiseptics.  We  must  not,  therefore,  depend  too 
much  upon  this  method,  which  once  seemed  so  rich  in  promises,  nor 
must  we  forget  that  the  best  antiseptics  are  those  which  are  secreted 
by  the  organism  itself.  The  efforts  of  the  physician  should,  therefore, 
be  directed  to  stimulate  the  reactions  of  the  system. 


THERAPEUTICS  OF  INFE0TI0U8  DI8EA8E8. 

Antitoxinic  Method. 

The  antiseptic  method  intended  to  destroy  germ  i  related  to  the 
antitoxinic  method  which  destroys  or  neutralize)  the  poi  on  .  We 
have  already  shown  thai  the  true  antitoxin  are  those  which  are 
secreted  by  the  animal  organism  in  the  cour  e  or  in  consequence  of 
infections.  There  are,  however,  pharmaceutical  ubstance*  capable 
of  neutralizing  certain  microbic  poisons.    We -hull  divide  them  into 

three  groups  .'recording  as  they  absorb  poisons,  precipitate  them,  or 

form  with  them  combinations  rendering  them  inoffensive. 

The  absorption  of  microbic  toxins  may  be  accomplished  by  mi 
of  charcoal  powder.  This  powder  fixes  noi  only  coloring  and  odorous 
substances,  but  it  possesses  the  power  of  retaining  alkaloids.  It  was 
supposed,  therefore,  especially  at  the  epoch  when  microbic  poisons 
were  believed  to  be  analogous  to  alkaloids,  that  the  ingestion  of  char- 
coal powder  would  diminish  intestinal  putrefaction.  This  is  what  has 
in  fact  taken  place.  This  medication,  however,  must  be  supple- 
mented by  prescribing  a  purgative  every  five  or  six  days,  in  order 
to  cleanse  the  intestine  of  the  accumulated  charcoal,  which  is  full  of 
toxins. 

Albumins  and  alkaloids  are  precipitated  by  certain  substances 
which  act  upon  these  two  groups  of  bodies.  Such  a  substance  is 
tannin.  It  may,  therefore,  be  hoped  that  this  medicine  will  prove 
useful  in  the  treatment  of  microbic  intoxications  by  rendering  harm- 
ful substances  insoluble.  In  fact,  the  employment  of  tannin,  tanni- 
gen,  or  tannalbin  gives  very  good  results  in  certain  digestive  infec- 
tions. In  the  course  of  putrefactions,  certain  chemically  well-defined 
substances  are  produced,  which  may  easily  be  neutralized.  Thus, 
sulphuretted  hydrogen,  which  is  so  often  originated  in  the  intestine, 
is  transformed  into  an  insoluble  sulphide  by  the  salts  of  bismuth. 
The  latter  medicine  acts  not  only  mechanically,  but  also  as  an  anti- 
toxic. 

It  may  also  be  asked  whether  poisons  cannot  be  neutralized  by 
certain  insoluble  precipitates  which  absorb  toxins.  Evidently  the 
poison  is  not  thus  destroyed,  and  experimentation  demonstrates  that 
the  combination  is  not  very  intimate,  since  the  precipitate  acquires 
noxious  properties.  Nevertheless,  possibly  some  part  of  it  is  neu- 
tralized in  this  manner,  which  would  be  a  favorable  result. 

When  toxins  combine  with  certain  bodies  they  become  less  toxic. 
This  is  notably  what  occurs  when  the}"  come  in  contact  with  iodine 


676  INFECTIOUS  DISEASES. 

and  its  derivatives.  The  action  of  iodine  and  trichloride  of  iodine 
has  been  well  demonstrated  by  numerous  experiments  bearing  espe- 
cially upon  tetanic  and  diphtheritic  toxins.  Probably  iodoform  acts 
in  the  same  manner.  The  latter  substance,  which  is  not  a  strong 
antiseptic,  gives  excellent  results  in  the  treatment  of  wounds,  because 
it  is  decomposed  and  liberates  iodine  which,  on  being  generated, 
unites  with  toxins  and  suppresses  their  action.  Carbolic  acid  seems 
to  act  similarly  by  neutralizing  the  tetanic  toxin.  Bacelli  has  advised 
the  injection  of  a  2  or  3  per  cent,  solution  of  carbolic  acid  beneath 
the  skin  of  tetanus  patients  during  twenty  days  or  more.  Each 
injection  is  to  be  3  eg.  to  4  eg.  Thirty  centigrams  of  carbolic  acid 
is  daily  introduced  in  addition  to  4  eg.  to  6  eg.  of  morphine.  This 
method  counts  at  present  a  certain  number  of  successes. 

Lastly,  if  we  remember  that  toxins  are  destroyed  by  oxidation,  we 
readily  understand  the  advantages  to  be  derived  from  oxidizing  sub- 
stances like  benzoate  of  soda.  Their  administration  acts  both  upon 
the  poisons  of  the  microbes  and  upon  those,  by  no  means  less  im- 
portant, which  are  originated  within  the  organism.  These  few  ex- 
amples show  how  interesting  it  would  be  to  pursue  investigations 
concerning  means  of  neutralizing  toxins  within  the  organism. 

This  antitoxic  method,  which  as  yet  includes  few  medicinal  sub- 
stances, assumed  great  importance  after  the  discoveries  of  Behring 
and  Kitasato.  The  majority  of  medicinal  serums  are  included  in  this 
group. 

Specific  Medication. 

Given  a  disease  to  find  a  remedy  to  cure  it  is  a  problem  laid  down 
by  the  ancients.  The  search  for  specifics,  the  preoccupation  of  which 
is  constantly  present  in  the  writings  of  Pliny,  persisted  until  a  recent 
epoch.  The  search  for  specifics,  which  was  nearly  abandoned  at  the 
time  experimentation  made  us  better  acquainted  with  the  mode  of 
action  of  medicines,  assumed  fresh  importance  with  the  discoveries 
of  serumtherapy.  The  medicinal  serum  is  the  specific  remedy  par 
excellence.  It  may  be  said  to  be  the  antidote  of  the  microbic  poison. 
The  antidiphtheritic  serum,  for  instance,  is  the  specific  medicine  of 
the  disease.  Its  injection  causes  the  pseudomembranes  to  exfoliate 
and  arrests  the  symptoms  of  intoxication.  The  fact  that  it  has  no 
influence  upon  identical  or  analogous  pseudomembranes  created  by 
other  pathogenic  agents  well  demonstrates  its  specific  action.  The 
employment  of  the  serum  is  not  only  the  best  treatment,  but  also 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  677 

represents  a  means  of  diagnosis.    It  confirms  the  old  adage '.NcUuram 
morborum  curationes  ostendunt. 

In  the  case  oi  8  therapeutic  serum  the  medicinal  lib  tance  repre- 
sents a  product  of  reaction  againsl  a  determined  toxin.  It  is,  there- 
fore, intelligible  thai  the  antitoxin  should  be  special  and  elective. 
[t  is,  however,  interesting  to  find  in  nature  vegetable  or  mineral 
substances  which  possess  an  analogous  property  and  are  bo  decidedly 
specific  that  they  iimy  equally  serve  diagnosis  and  treatment.  The 
specific  action  is,  however,  less  clear.  Although  each  of  these  sub- 
stances cures  one  disease,  they  are  capable  of  improving 
others,  or  at  least  combating  certain  symptoms. 

Aside  from  therapeutic  serums,  we  are  aj  presenl  acquainted  with 
four  specific  substances:  cinchona,  mercury,  iodine,  and  salicylic 
acid. 

Cinchona  and  Quinine.  The  febrifuge  action  of  cinchona  bark 
seems  to  have  been  observed  long  ago  by  the  inhabitants  of  Peru. 
It  was  not,  however,  known  in  Europe  until  after  the  middle  of  the 
eighteenth  century.  The  remedy  was  introduced  by  the  Com 
El  Cinchon,  Vice-queen  of  Peru,  and  almost  coincidently  by  the 
Jesuit  missionaries.  It  was  at  first  known  under  the  designation 
"Countess'  powder"  and  "Jesuits'  powder."  In  1679,  Louis  XIV. 
bought  from  the  Englishman,  Talbot,  the  secret  of  a  febrifuge  remedy 
which  was  nothing  else  than  a  wine  prepared  with  cinchona  bark. 
It  was  not  until  the  next  century,  in  1737,  that  La  Condamine  and 
Joseph  of  Jussieu  determined  the  cinchona  tree.  Finally,  in  1820, 
Pelletier  and  Caventou  succeeded  in  extracting  the  principal  alkaloid 
of  cinchona — quinine. 

Cinchona  or  quinine  is  not  a  common  antipyretic  medicine.  It  is 
first  of  all  a  specific  antipyretic  acting  upon  malarial  fevers.  The 
employment  of  the  medicine  was  regulated  by  Torti  and  Sydenham. 
The  method  of  Torti,  which  consisted  in  administering  the  drug 
before  the  paroxysm,  was  abandoned  by  its  author,  who  adopted 
Sydenham's  or  the  English  method,  the  essential  principle  of  which 
was  to  give  cinchona  at  the  end  of  the  paroxysm.  It  is  known  that 
quinine  was  abandoned  under  the  influence  of  Broussais*  ideas  or 
was  given  in  insufficient  doses,  and  the  fearful  reign  of  malarial  fever 
in  the  troops  of  Algeria  is  not  forgotten.  At  the  present  day  quinine 
is  generally  prescribed  in  one-half  to  one  gram  doses.  Two  or  three 
grams  is  but  exceptionally  reached.  It  should  be  administered  either 
after  the  paroxysm  or  five  or  six  hours  before  its  return.    The  latter 


678  ISFECTIOUS  DISEASES. 

method  is  the  more  usual  one.  Laveran  advises  its  administration 
for  three  days  in  doses  of  one-half  to  one  gram  (hydrochlorate  of 
quinine),  then  in  doses  of  60  eg.  to  SO  eg.  on  the  eighth,  ninth,  and 
tenth  days,  and  a  renewal  of  the  same  prescription  on  the  fifteenth, 
sixteenth,  twenty-first,  and  twenty-second  days. 

Since  the  researches  of  Binz  it  is  known  that  quinine  salts  exert 
a  harmful  action  upon  ameba?.  They  are  powerless  against  plants 
of  a  low  organization,  while  they  rapidly  destroy  protozoa.  By 
mixing  a  drop  of  blood  containing  hematozoa  with  a  drop  of  a  weak 
quinine  solution  we  may  see  how  rapidty  the  movements  of  the 
pigmentary  grains  and  the  motile  filaments  are  arrested.  The  fever 
may  recur,  because  quinine,  which  kills  the  adult  hematozoa,  acts 
with  much  less  energy  upon  the  encysted  germs  of  these  parasites. 
Thus,  quinine  represents  a  specific  medicine  belonging  to  the  group 
of  germicidal  drugs.  It  is  a  parasiticide.  This  is  a  very  important 
fact,  but  it  would  not  be  safe  to  generalize  the  conclusion.  It  seems 
probable,  however,  that  such  is  also  the  case  with  mercury — that 
this  substance  acts  in  syphilis  as  a  parasiticide. 

Mercury  and  Iodine.  It  was  not  by  chance,  as  has  been  asserted 
by  Fallope,  that  mercury  was  first  employed.  It  had  long  been 
praised  by  the  Arabs  in  the  treatment  of  leprosy.  It  was  in  use 
against  parasites,  pedicular  affections,  and  the  itches.  It  was 
tried  in  sj^philis  by  analogy.  Employed  for  the  first  time  by  Wich- 
mann  in  1497,  it  was  particularly  praised  by  Berenger  (of  Carpi)  and 
Jean  de  Vigo,  who  prescribed  it  in  the  form  of  plasters;  by  Fracaster, 
who  employed  it  in  friction,  and  by  Matthioli,  who  administered  it 
internally.  At  present  mercury  is  administered  by  the  digestive  canal 
or  by  inunctions,  by  subcutaneous  or  intramuscular  injection,  and, 
in  grave  cases,  by  intravenous  injection.  We  may  employ  metallic 
mercury  (blue  pill,  Sedillot's  pills,  inunctions  with  Neapolitan  ungu- 
entum,  injections  of  mercury,  etc.),  the  insoluble  salts  (pill  of  proto- 
iodide,  injections  of  calomel),  the  soluble  salts,  notably  corrosive 
sublimate  (Dupuytren's  pills,  Van  Swieten's  solution),  biniodide 
(biniodizeel  oils),  peptonate,  benzoate,  and  cyanide.  The  soluble 
salts  are,  of  course,  used  for  intravenous  injection.  Sometimes  cor- 
rosive sublimate  is  employed  in  doses  of  1  mg.  to  8  mg.;  oftener 
cyanide  of  mercury. 

The  powerful  antiseptic  properties  of  mercury  salts  lead  to  the 
presumption  that  this  medicine  acts  upon  the  pathogenic  agents  of 
syphilis.     Direct  experimentation  being  impracticable,  hypotheses 


THEMAPEUTICS  OF  INFECTIOUS  DISEASES.  670 

have  been  advanced,  It  is  well  to  notice,  however,  thai  the  question 
is  undoubtedly  one  of  specific  action,  for  mercury  doe  nol  acl  imi- 
larly  against  other  infections.  On  the  other  hand,  il  i  nol  equally 
useful  against  all  syphilitic  tnanife  tation  .  [n  the  prima] 
i Mercury  acts  upon  the  chancre  and  adenites.  tts  action  is  still  more 
marked  upon  the  secondary  manifestations.  General  treatment 
makes  them  disappear;  local  breatmenl  often  suffice*  to  cure  them. 

We  must  recognize,  however,  thai  the  specific  action  of  mercury 
Is  not  perfed .  Certain  manifestations  are  bul  slighl  ly  modified  under 
its  influence.  The  generalized  disturbances  of  the  secondary  period, 
syphilitic,  fever,  syphilitic  anemia,  pseudochlorosis,  and  secondary 
cephalalgia  fm|u<Mitly  resist  Its  action.  Likewise,  more  profound 
manifestations,  tubercular  and  pustular  syphilides,  and  precocious 
gummata  require  complementary  treatment.  Finally,  at  a  late 
period,  mercury  is  insufficient.  In  all  such  cases  recourse  should 
be  had  to  another  specific,  advised  for  the  firsl  time  in  L836  by 
Wallace  (of  Dublin),  and  the  indications  for  which  have  been  well 
regulated  by  Ilicor.  We  refer  to  iodine  in  the  form  of  iodide  of 
potassium.  Thus  we  have  two  specifics  for  one  disease,  and,  a  fact 
of  particular  interest,  each  of  these  substances  has  its  peculiar  indi- 
cations, so  that  they  must  be  employed  successively  or  in  conjunc- 
tion, as  the  case  may  be. 

The  iodide  is  not  infallible.  There  are  cases  on  record  in  which 
treatment  regularly  followed  produced  no  effect.  The  author  ob- 
served a  young  man  suffering  from  an  indurated  chancre.  Being 
the  relative  of  a  very  distinguished  physician,  he  was  treated  from 
the  very  beginning  and  submitted  to  mercurial  medication.  Two 
years  later  he  suffered  from  ocular  disorders.  One  of  the  ablest 
ophthalmologists  of  Paris  prescribed  the  mixed  treatment  for  him. 
Instead  of  the  improvement  expected  from  an  energetic  treatment, 
symptoms  of  spinal  syphilis  made  their  appearance.  In  spite  of  all 
the  medication  employed,  in  spite  of  the  iodides,  in  spite  of  mercury 
injected  in  the  form  of  cyanide  into  the  veins,  the  paralysis  followed 
an  ascending  course,  and  terminated  fatally  with  the  appearance  of 
bulbar  phenomena.  Facts  of  this  kind  are  rare,  but  are  not  alto- 
gether exceptional.  In  the  presence  of  them  doubt  has  been  ex- 
pressed as  to  the  efficiency  of  mercury  and  potassium  iodide.  The 
doubt  is  not  well  founded.  Treatments,  even  when  specific,  do  not 
always  succeed.  Clinical  phenomena  are  too  complex  to  be  covered 
by  a  single  formula  explaining  their  entire  evolution.    Deaths  occur 


680  INFECT  JO  US  DISEA  SES. 

from  syphilis  in  spite  of  mercury  and  iodide,  as  people  die  from 
diphtheria  in  spite  of  antidiphtheritic  serum.  We  have  reason  to 
be  highly  satisfied  that  it  is  possible  to  cure  the  great  majority  of 
sufferers. 

It  is  hardly  necessary  to  say  that  specific  treatment  has  no  action 
upon  the  common  lesions  consecutive  to  syphilitic  lesions.  Although 
it  may  still  improve  certain  scleroses,  it  is  evidently  incapable  of 
removing  lesions  produced  by  stricture  or  obliteration  of  arteries, 
fibrous  cicatrices,  and  foci  of  softening. 

We  need  not  dwell  at  length  upon  the  necessity  of  having  two 
specifics  for  one  disease.  One  hypothesis  alone  seems  plausible.  It 
may  be  admitted  that  the  agent  of  syphilis  undergoes  profound  modi- 
fications within  the  organism  which  it  has  invaded.  Although  very 
virulent  in  the  beginning,  as  is  evident  from  the  contagiousness  of 
the  primary  and  secondary  manifestations,  the  agent  gives  rise  only 
to  superficial  lesions.  Later  it  possesses  very  slight,  if  any,  virulence, 
and  yet  at  this  period  of  its  evolution  it  seems  to  be  more  dangerous 
for  the  organism.  It  becomes  localized  at  various  points  and  pro- 
duces reactions  unlike  those  of  the  former  periods.  There  seems  to 
be  no  apparent  analogy  between  a  papular  syphilide  and  a  gumma. 
The  reason  the  reactions  of  the  organism  which  produce  the  lesion 
are  so  dissimilar  is  evidently  that  the  parasite  is  modified  or  that  the 
organism,  being  gradually  impregnated  with  the  toxins,  has  under- 
gone a  profound  transformation.  In  the  two  cases,  the  manifesta- 
tions being  no  longer  analogous,  the  necessity  of  two  different  treat- 
ments is  readily  conceivable. 

We  must  here  recall  that  iodine  is  not  a  specific  for  syphilis  alone. 
Without  speaking  of  its  action  upon  scrofulosis,  there  is  another 
infection  in  which  iodine  is  a  specific,  namely,  actinomycosis. 
Thomasses,  of  Utrecht,  was  the  first  to  show  that  potassium  iodide 
may  cure  actinomycosis  in  animals.  Nocard  made  it  known  in 
France.  Then  successful  attempts  were  made  in  man  by  Van  Hersen 
and  others.  Netter,  Duguet,  and  Ducor  have  reported  interesting 
observations.  The  favorable  effects  usually  become  manifest  when 
phenomena  of  iodism  appear. 

Salicylic  Acid.  Salicylic  acid  and  its  derivatives  are  often  spoken 
of  as  specifics  for  acute  articular  rheumatism. 

Maclagan  tried  salicin  in  1874.  He  started  from  the  idea  that  the 
willow,  growing  in  damp  countries,  where  rheumatism  is  frequent, 
must  contain  some  antirheumatic  substance,  since  cinchona,  which 


THERAPEUTICS  OF  INFECTIOUS  DISEA8E8,  C,H] 

grows  in  malarial  countries,  contain    a  febrifuge  sub  tance.     Bu 
called  attention  bo  salicylic  acid.    Strieker  showed  the  good  <■' 
of  the  substance  (1876),  for  which  Senator  Bub  tituted  salicylate  of 
soda.    At  present  the  lasl  named  medicine  and  certain  similar  sub- 
stances, such  as  salol,  salipyrine,  Balophen,  and  aspirin,  are  employed. 
Methyl  salicylate  is  used  for  external  applications. 

All  these  preparations  give  excellent  re  nil  .    Are  they,  • 
true  specific  medicaments?    A  greal  many  authorities  so  believe,  and 
argue  that  those  arthrites  which  resisl  the  action  of  the  medicine  are 
not  truly  rheumatic.    In  fact,  il  is  certain  thai  the  arthropathy 
secondary  infections,  notably  gonorrheal  arthropal  nies,  are  nol  bene- 
fited by  salicylates  as  are  the  arthropathies  of  acute  articular  rheu- 
matism.   This  is  an  argumenl  in  supporl  of  the  specific  character. 
II,  has  been  objected  thai  the  visceral  manifestations  occurring  in  the 
course  of  their  evolution  arc  not  modified,  bu1  we  have  -ecu  analog 
results  in  many  other  oases.    Specific  serums  are  likewise  powerless 
to  remedy  certain  visceral  evolutions,  such  as  nephritis  and  parab 
We  may,  therefore,  class  the  salicylates  among  the  specific  medicine-, 
although  it  must  be  acknowledged  that  we  are  completely  ignorant 
of  their  mode  of  action. 

If  we  now  consider  the  four  specific  medicines,  we  see  that  one 
of  them — quinine — acts  as  a  parasiticide,  and  that  the  other  three 
possess  an  influence  the  mechanism  of  which  remains  unknown. 

Bacteriotherapy. 

Bacteriotherapy  is  a  therapeutic  method  aiming  to  combat  infec- 
tion by  infection,  viz.,  to  introduce  virulent  agents  or  microbic  toxins 
into  the  diseased  organism. 

It  has  been  long  known  to  clinical  observers  that  erysipelas  may 
cause  torpid  infectious  lesions  to  retrocede  and  disappear.  Ulcers, 
lupus,  syphilitic  lesions,  and  cancer  have  been  seen  to  improve  and 
heal  under  the  influence  of  an  intercurrent  erysipelas.  It  may. 
therefore,  be  questioned  whether,  in  certain  cases,  it  would  not  be 
advisable  to  inoculate  disease  for  therapeutic  purposes.  Ricor 
made  the  first  attempt  of  this  kind  in  syphilis.  The  method  proved 
unsuccessful,  and  experiments  of  this  nature  have  only  recently 
been  taken  up.  Following  Fehleisen.  several  physicians  injected 
cultures  of  living  and  virulent  streptococcus  into  patients  suffering 
from  cancer.  The  procedure  was  a  dangeious  one.  Several  of  the 
patients    thus    treated   succumbed.      Nevertheless,    inoculation    of 


682  INFECTIO  US  DISEASES. 

virulent  products  is  still  employed  in  one  case,  namely,  in  the  treat- 
ment of  pannus;  the  introduction  of  gonorrheal  pus  induces  a 
purulent  conjunctivitis  which  is  sometimes  followed  by  a  cure. 

While  virulent  microbes  are  dangerous,  non-pathogenic  microbes 
may  be  introduced  with  apparent  safety.  An  attempt  has  been 
made  to  treat  tuberculosis  by  inhalations  of  the  bacterium  termo. 
The  results  were  negative,  and  the  procedure  was  abandoned.  A 
therapeutic  measure  has  recently  been  resorted  to  which  enters  the 
domain  of  bacteriotherapy.  We  refer  to  the  ingestion  of  beer  yeast 
against  suppurative  cutaneous  inflammations  and  notably  furuncu- 
losis. 

This  method,  which  was  indicated  as  early  as  1852  by  an  English 
physician,  Mosse,  is  a  popular  remedy  in  the  north  of  France. 
It  has  been  employed  by  Debouzy,  Gobert,  and  De  Backer.  It  is 
only  since  the  work  of  Dr.  Brocq,  however,  that  attention  has  been 
drawn  to  this  subject.  The  investigations  of  this  author  show  that 
by  giving  to  a  patient  one  teaspoonful  of  fresh  yeast  three  times  a 
day  we  ma)^  arrest  the  development  of  furuncles,  suppress  pain,  and 
hasten  cicatrization.  It  is  not  exactly  known  how  the  yeast  acts. 
It  probably  produces  its  effect  by  regulating  digestion,  which  is  so 
often  disturbed  in  these  patients. 

The  employment  of  living  microbes  for  therapeutic  purposes  seems 
to  have  a  rather  restricted  field.  As  microbes  do  not  act  except 
by  their  soluble  products,  it  may  be  questioned  whether  toxins 
might  not  render  the  same  therapeutic  service.  We  must  consider 
two  quite  different  cases.  We  may  combat  an  infection  by  means 
of  products  originated  by  microbes  different  from  the  one  which 
we  wish,  to  antagonize.  On  the  other  hand,  we  may  employ  the 
toxins  secreted  by  the  pathogenic  microbe  which  we  wish  to  attack. 
The  former  method  is  very  much  like  bacteriotherapy,  which  has 
already  been  studied.  There  are  some  experiments  in  its  support. 
When  speaking  of  microbic  associations  we  alluded  to  the  fact  that 
pyocyaneus  toxins  hinder  the  evolution  of  anthrax.  Sterilized 
cultures  of  the  bacillus  prodigiosus  act  in  the  same  manner,  at 
least  in  rabbits.  Kostiurine  and  Krainski  have  shown  that  putrefied 
fluids  combat  anthrax  and  tuberculosis.  Therapeutic  attempts  were 
made  on  man.  Rumpf  and  Kraus  have  treated  typhoid  cases  by 
sterilized  cultures  of  the  bacillus  pyocyaneus. 

Streptococcic  Toxinotherapy.  Cultures  of  the  streptococcus 
have  been  the  subject  of  the  greatest  number  of  researches.    Lassar, 


THERAPEUTICS  OF  TNFE0TI0U8  DISEASES.  683 

Spronck,  Coley,  Friedreich,  Kocher,  and  R4pin  treated  a  certain 
number  of  neoplasms  by  means  of  streptococcic  toxin  and  obtained 
a  few  successes,  especially  in  cases  of  sarcomata.    The  procedures 

employed  |>y  these  various  observers  were  not,  however,  alwayfi  the 

same. 
Lassar,1   fearing  the  use  of  simply   filtered  cultures,   the  high 

toxicity  of  which  we  h.-ive  proved  ;is  regards  animals,  resorted  to 
cultures  sterilized  by  heal  and  freed  from  all  figurate  elements  by 
means  of  filtration  through  porcelain.    The  greatesl   pari  of  the 

noxious  substances  is  thus  destroyed,  and  the  fluid  is  not  toxic 
unless  it  is  derived  from  an  extremely  virulent  culture.  Taking 
ground  upon  the  same  experimental  facts,  Spronck*  also  tried  the 
heated  cultures.  Believing,  however,  t hat  the  toxic  substances 
would  be  more  active  from  a  therapeutic  standpoint,  he  employed 
a  mixture  of  heated  and  simply  filtered  cultures.  Etepin"  employed 
filtered  but  not  heated  cultures.  Finally,  Coley,'  inspired  by  our 
investigations  on  microbic  associations,  utilized  a  mixture  of  strepto- 
coccic toxins  and  sterilized  cultures  of  the  bacillus  prodigiosus. 
Not  only  the  composition  of  the  fluid,  but  also  the  mode  of  injection 
varied.  While  Lassar  and  Coley  injected  the  toxins  into  the  interii  ir 
of  the  tumors,  Spronck  and  Repin  injected  them  at  a  distant  point, 
and  Repin  finally  introduced  them  into  the  veins.  These  various 
procedures  having  given  a  few  successes  in  the  treatment  of  neo- 
plasms, we,  with  Dr.  Hallopeau,5  pursued  analogous  researches  upon 
lupus.  It  seemed  to  us,  however,  that  our  first  duty  was  to  begin 
with  harmless  fluids — i.  e.,  to  try  streptococcic  cultures  sterilized 
by  heat. 

We  operated  in  the  following  manner:  Bouillon  containing  a 
streptococcus  of  medium  virulence  was  kept  in  the  incubator  for 
fifteen  days.  At  the  end  of  this  period  the  culture  was  evaporated 
and  reduced  to  one-sixth  of  its  original  volume,  then  heated  in  the 
autoclave  to  230°  F.  (110°  C.)  for  fifteen  hours.  The  culture  was  not 
filtered,  in  order  that  we  might  use  both  the  toxins  modified  by  heat 

1  Lassar.     Zur  Erysipclimpfung.     Deutsche  med.  Wochenschrift.  1S91.  Xo.  29. 

2  Spronck.  Tumeurs  malignes  et  maladies  infectieuses.    Annales  de  l'Lnstitut  Pasteur, 
1S92,  p.  6S3. 

3  Repin.     La  toxithe>apie  des  tumeurs  malignes.     Revue  de  chirurgie,  June,  1S95, 
p.  465. 

4  Coley.     Treatment  of  Inoperable  Malignant   Tumors  with  the  Toxin  of  Erysipelas 
and  the  Bacillus  Prodigiosus.     American  Journal  of  the  Medical  Sciences.  July.  I - 

6  Hallopeau  and  Roger.    Action  des  toxines  streptococciques  sur  le  lupus.    La  presse 
m£dicale,  April  S,  1S96. 


684  INFECTIOUS  DISEASES. 

and  the  microbic  cadavers.  The  fluid  thus  obtained  is  almost 
inoffensive.  Guinea-pigs,  rabbits,  and  mules  received  considerable 
amounts  without  presenting  any  notable  disturbance.  We  kept  for 
two  years  a  rabbit  which  had  received  400  c.cm.  of  sterilized 
streptococcic  toxins  and  which  continued  in  good  health.  It 
seemed,  therefore,  that  the  fluids  were  not  apt  to  give  rise  at 
the  end  of  a  certain  period  of  time  to  any  organic  disturbances  or 
visceral  lesions.  The  only  phenomena  produced  in  the  animals  by 
subcutaneous  injections  were  tumefaction  at  the  point  inoculated 
and  sometimes  a  transitory  rise  in  temperature.  There  are  some 
exceptions,  however,  to  this  rule.  An  animal  may  manifest  an 
active  reaction,  while  other  animals  present  no  disorder  whatever. 
We  observed  a  mule  in  which  each  injection  of  the  toxin  produced 
fever,  profuse  sweating,  and  lassitude,  while  other  mules  similarly 
inoculated  showed  no  reaction.  The  same  individual  peculiarities 
are  more  markedly  observed  when  man  is  experimented  upon. 

Our  therapeutic  inoculations,  which  were  practised  upon  seven 
women,  were  all  made  into  the  diseased  regions,  beneath  the  skin. 
We  began  by  injecting  five  or  six  drops  of  the  fluid,  representing 
thirty  to  thirty-six  drops  of  the  primary  culture;  then,  if  the  sensi- 
tiveness of  the  patient  was  not  too  great,  we  gradually  increased 
the  dosage.  We  finally  introduced  as  many  as  thirty  drops  of 
toxins  at  one  sitting,  about  9  c.cm.  of  the  culture.  The  injection 
generally  caused  a  sufficiently  strong  local  reaction.  An  edematous 
tumefaction,  a  true  fluxion,  was  generally  produced,  which  set  in 
from  fifteen  minutes  to  two  or  three  hours  after  the  injection.  The 
edema  was  in  some  cases  sufficiently  intense  to  disturb  the  patient 
and  notably  to  cause  closure  of  the  eyelids,  or  to  embarass  move- 
ment of  the  lips.  At  the  end  of  a  few  hours,  however,  the  symptoms 
improved,  and  within  a  day  or  two  the  edema  disappeared  alto- 
gether. These  local  manifestations  evidently  vary  according  to  the 
amount  introduced.  Individual  predisposition,  however,  seems  to 
play  the  principal  role  in  their  production.  In  one  of  our  patients 
the  smallest  injection  gave  rise  to  tumefactions  which,  at  first, 
seemed  quite  disquieting.  In  spite  of  the  local  disorders,  the  general 
phenomena  were  not  very  pronounced.  A  few  patients  complained 
of  malaise  and  lassitude,  several  of  lumbar  pains  for  a  day  or  two. 
Contrary  to  what  has  been  noted  by  other  observers,  however,  we 
noticed  no  veritable  fever.  The  temperature,  carefully  taken  every 
hour,  did  not  rise  above  99.5°  F.  (37.5°  C).    Only  once  a  patient 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  685 

developed  a  temperature  of  104°  r.  (40°  C).  The  intere  ting  fad 
in  this  case  was  that  the  hyperthermia  was  produced  a1  the  end  of 
two  months  of  treatment,  while  previous  injections  of  practically 
the  same  amounts  had  given  rise  to  no  fever,  nor  did  subsequent 

inoculations. 

II,  did  not  seem  to  us  that  a  well  marked  habil  to  the  toxin* 
produced.    The  Local  phenomena  were  nearly  always  the  Bame  in 
the  same  patient.     In  the  woman  who  i  resented  3uch  a  remarkal  le 
susceptibility  the  reactional  swelling  was  produced   al  the  end  of 

nine  months  of  treatmenl  just  as  on  the  first  day.  This  result, 
which  differs  notably  from  tint  obtained  by  other  experimenters, 
is  due,  perhaps,  to  the  presence  of  inicrobic  radavers  in  the  liquid 
employed,  perhaps   to   the  relatively   long  interval   between   the 

injections;  in  fact,  the  hit  lei'  were  given  only  once  ;i  week. 

The  action  of  sterilized  cultures  of  the  bacillus  prodigiosue 
quite  different.  This  microbe  was  cultivated  in  bouillon,  then,  at 
the  end  of  eighl  days,  the  culture  was  sterilized  at  a  temperature 
of  230°  F.  (110°  C.)  for  ten  minutes  and  injected  without  being 
filtered.  The  fluid  thus  prepared,  mixed  with  the  streptococcic 
culture,  was  tried  on  four  patients.  We  began  by  introducing  three 
drops  of  the  culture  of  bacillus  prodigiosus.  This  minute  dose  cause*  1 
accidents  which  somewhat  alarmed  us,  at  least  with  regard  to  two  of 
the  patients.  Three  hours  after  the  injection  violent  chills  occurred, 
the  extremities  became  cold,  the  pulse  was  weak  and  rapid,  the 
central  temperature  rose  to  102.2°  F.  and  to  103.1°  F.  (39°  and 
39.5°  C);  these  symptoms  were  followed  by  nausea,  vomiting  and. 
in  one  of  the  patients,  diarrhea  with  incontinence  of  feces.  These 
disorders,  however,  were  only  transitory.  On  the  following  day  the 
patients  simply  felt  tired.  The  crisis  terminated  in  a  very  profuse 
herpes  labialis.  Instructed  by  these  results,  we  introduced  only  two 
drops  of  the  culture  for  the  second  injection.  The  symptoms  con- 
sisted in  a  slight  malaise  and  an  insignificant  rise  in  temperature. 
Subsequently  the  patients  became  habituated  to  the  toxin,  and 
received  progressively  increasing  doses — as  many  as  six  drops — 
without  presenting  any  appreciable  reactions. 

The  action  of  the  bacillus  prodigiosus  demonstrated  far  better 
than  all  laboratory  experiments  that  a  minute  dose  of  toxin  may 
give  rise  to  extremely  grave  general  manifestations,  and  clearly 
establishes  the  toxi-infectious  origin  of  herpes.  Lastly,  it  is  very 
interesting  to  note  that  the  soluble  products  of  the  bacillus  pro- 


686  INFECTIOUS  DISEASES. 

digiosus  and  non-pathogenic  microbes  proved  far  more  toxic  than 
those  of  the  streptococcus.  The  differences  were  very  remarkable. 
Three  drops  of  the  bacillus  prodigiosus  produced  disquieting  symp- 
toms, while  thirty  drops  of  a  streptococcic  culture,  representing 
9  c.cm.  of  the  primary  culture,  produced  only  a  local  reaction. 
Sterilization,  however,  had  been  made  according  to  the  same  pro- 
cedure, viz.,  by  heat  at  210°  F.  (110°  C). 

If  now  we  consider  the  results  obtained  in  our  seven  patients 
we  find  that  in  one  lupus  was  completely  cured.  In  two  a  very 
marked  improvement  was  produced;  in  the  other  four,  amelioration 
was  slight  or  nil.  The  best  results  were  obtained  in  young  subjects, 
whose  vital  reaction  is  more  energetic  and  more  readily  aroused, 
and  in  those  whose  lupuses  were  characterized  by  fungous,  vegetat- 
ing tubercles  and  deep  and  extensive  ulceration.  Under  the  influ- 
ence of  the  treatment  the  tubercles  were  reduced,  the  discharges 
disappeared,  and  the  ulcerations  rapidly  diminished.  Finally,  there 
was  produced  a  cicatrix  remarkable  for  its  perfect  elasticity;  it  was 
almost  normal  skin.  On  the  other  hand,  the  result  was  slight  or 
negative  in  those  cases  in  which  sclerosis  dominated  and  the  tubercles 
were  embedded  in  cicatricial  tissues.  All  that  was  observed  in  such 
patients  was  a  reduction  in  the  size  of  the  tubercles  and  disappear- 
ance of  a  few. 

The  results  obtained  by  us  will,  perhaps,  not  appear  very  encour- 
aging. The  patients,  however,  manifested  great  enthusiasm  with 
regard  to  these  therapeutic  attempts.  In  despair  at  the  failure  of 
other  methods,  the  sufferers  were  satisfied  with  the  amelioration 
obtained  at  our  hands.  The  reason  we  did  not  further  pursue  our 
attempts  is  that  microbic  toxins  are  such  actively  energetic  sub- 
stances that  one  cannot  exercise  too  much  prudence  when  applying 
them  to  human  therapeutics.  We  would  not  have  made  even  the 
attempts  above  reported  had  we  not  been  led  to  do  so  by  laboratory 
investigations  and  by  results  obtained  in  the  treatment  of  cancer. 
At  all  events,  we  watched  the  patients  with  the  greatest  care.  We 
repeatedly  examined  their  urine  and  we  prolonged  the  experiment 
because  we  noticed  no  permanent  disorder  and  no  albuminuria. 
The  results  obtained  did  not  seem  to  us,  however,  sufficiently  satis- 
factory for  continuing  our  therapeutic  attempts.  Nevertheless,  we 
thought  it  might  be  of  value  to  make  known  our  researches  in  the 
hope  that,  if  taken  up  by  others  with  some  technical  modifications, 
they  would  lead  to  a  better  method.     The  method  should  be  so 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  687 

modified  ;is  to  increase  the  local  action  and  i"  Buppre  the  general 
manifestations.  In  fact,  it  seems  thai  tli''  toxin  acl  by  the  inflam- 
mation induced  by  them;  and  it  i  for  thi  rea  on  thai  we  injected 
them  into  the  diseased  tissue  itself.  Whal  proves  thai  we 
right  in  so  doing  is  the  fad  thai  in  ;i  case  of  bilateral  lupus  the 
inoculated  side  rapidly  improved,  while  the  oppo  ite  ide  pre  ented 
bill  slight  modification.  Moreover,  for  fear  of  accidents,  we  made 
only  one  injection  per  week.  It  is  better  t<>  make  one  every  two 
or  three  days.  Lastly,  our  observations  showed  thai  the  addition 
of  soluble  producls  of  Hie  b;ieillus  |trodigiosus  render  the  fluids 
much  more  efficacious.  In  ;i  ca.se  in  which  the  Streptococcic  toxins 
were  employed  alone  the  results  were  almosl  nil.  Each  injection 
however,  produced  very  m:irl«-d  edema  in  the  patient.  For  this 
reason  we  did  not  add  the  bacillus  prodigiosus,  and  noted  thai 
fluxions  caused  by  the  streptococcus  alone  were  not  sufficient  to 
ameliorate  lupus.  Likewise,  in  the  patient  who  recovered  and  in 
those  who  notably  improved,  the  favorable  effects  were  not  very 
clear  until  after  the  mixture  of  the  two  toxins  was  employed. 

It  is  not,  however,  to  be  concluded  that  these  microbic  products 
possess  specific  germicidal  power.  The  toxins  probably  act  not 
upon  the  bacillus,  but  upon  the  organism.  They  stimulate  the 
responsive  activity  of  the  economy  and  attract  to  the  diseased  spot 
serum  and  leucocytes  which  combat  the  bacilli  and  the  morbid  tissue 
developed  under  their  influence. 

While  the  results  obtained  are  not  sufficiently  successful  to 
warrant  a  systematic  continuance  of  the  bacteriotherapic  method, 
it  would  be  reasonable  to  try  it  in  certain  suitable  cases,  viz..  in 
young  persons  suffering  from  fungus  and  ulcerating  forms  of  lupus. 
We  are  aware  that  cases  of  this  variety  are  most  frequently  cured 
by  classical  procedures.  When,  however,  the  latter  fail,  a  last 
attempt  may  be  made  by  means  of  the  toxins.  It  is  well  to  repeat 
that  it  is  necessary  to  increase  the  therapeutic  effects  by  practising 
the  injections  at  shorter  intervals  and  by  employing  more  active 
fluids,  or  by  making  use  of  a  serum  analogous  to  that  which  was 
employed  by  Emmerich  and  Scholl  in  the  treatment  of  cancer. 

Streptococcic  Hematoxin.  Instead  of  a  culture,  Emmerich  and 
Scholl  employed  the  serum  of  infected  animals.  One  might  suppose, 
in  fact,  that  active  toxins  would  be  found  therein  in  greater  abun- 
dance. 

The  serum  of  sheep  infected  with  the  streptococcus  was  filtered 


688  INFECTIOUS  DISEASES. 

through  porcelain  in  order  to  free  it  from  all  living  elements.  This 
serum  was  injected  into  neoplasms  in  doses  varying  from  1  c.cra  to 
25  c.cm.  The  injections  produced  at  the  point  of  inoculation  a  red- 
ness analogous  to  that  of  erysipelas,  which  persisted  for  a  day  or  two. 
A  febrile  movement  was  at  the  same  time  observed.  It  is  to  be 
noted  that  the  more  intense  the  local  reactions  the  better  were  the 
effects  produced.  Such  is  precisely  the  case  when  sterilized  cultures 
are  made  use  of.  The  serum  proved  inefficient  in  only  two  cases. 
In  the  other  patients  the  more  recent  the  tumor  the  greater  was 
the  activity  of  the  serum.  Its  employment  is  advisable  in  cases 
of  postoperative  relapses. 

The  report  of  Emmerich  and  Scholl  was  too  important  not  to 
immediately  give  rise  to  control  researches.  Unfortunately,  the 
results  obtained  by  other  experimenters  were  not  confirmative. 
Some  of  them,  Schuler  among  others,  reported  successes,  but  the 
majority  of  physicians  obtained  no  appreciable  results,  and  some 
of  them  even  observed  accidents.  Burns  found  the  patients  feverish 
and  dyspneic,  the  heart  weakened  and  the  urine  albuminous.  In 
spite  of  the  answers  given  by  Emmerich  and  Scholl  to  criticisms, 
their  method  is  to-day  abandoned.  It  does  not  seem  to  be  superior 
to  bacteriotherapy,  and  it  has  the  disadvantage  of  being  more 
complicated  and,  what  is  of  greater  consequence,  more  dangerous. 

Tuberculin.  The  method  that  consists  in  treating  an  infection 
by  the  soluble  products  engendered  by  the  pathogenic  agent  which 
is  to  be  combated  differs  considerably  from  the  toxinotherapic 
procedure  above  studied.  The  latter  is  based  upon  experimental 
data;  such  is  not  the  case  with  the  former.  In  fact,  numerous 
investigations  have  demonstrated  that  microbic  products  favor  the 
development  of  the  microbe  which  has  secreted  them.  .  Although 
they  are  often  endowed  with  vaccinating  power,  they  are  never 
curative.  Perhaps  it  will  some  day  be  possible  to  prepare  a  sub- 
stance possessing  therapeutic  properties  by  modifying  these  prod- 
ucts. This  is  what  Smirnow  claims  to  have  obtained  by  subjecting 
diphtheritic  toxin  to  electrolysis. 

Microbic  products  have  been  utilized  in  the  treatment  of  three 
diseases— tuberculosis,  glanders,  and  typhoid  fever. 

The  enthusiasm  with  which  the  first  communication  of  Koch  was 
met  is  well  remembered.  At  the  Berlin  Congress  of  1890  the  eminent 
scientist  announced  that  he  had  succeeded  in  arresting  the  evolution 
of  tuberculosis  in  animals  by  means  of  a  product  which  was  called 


THERAPEUTICS  OF  TNFEOTI0U8  DI8EA8E8. 

tuberculin  or  Koch's  "lymph."  If  can  be  prepared  by  reducing 
bo  one-tenth  of  its  volume  a  culture  of  tubercle  bacilli  developed 
in  glycerinated  peptonized  veal  bouillon,  When  filtered  through 
porcelain  it  is  obtained  in  the  form  of  s  limpid  and  brownish  fluid, 
the  composition  of  which  is  evidently  quite  variable.  Hence,  \\ 
should  not  be  employed  excepl  after  its  action  ha  been  verified 
upon  tubercular  guinea-pigs. 

Like  oilier  microbic  products,  tuberculin  act*  only  when  ii  i 
injected  beneath  the  skin  or  into  the  veins.  When  introduced  by 
the  alimentary  canal  it  has  no  effect.  Us  action  is  not  very  marked 
upon  animals;  a  guinea-pig  easily  resists  2  c.cm.  of  the  "lymph," 
while  ;i  dose  of  0.25  c.cm.  produces  notable  effects  in  man.  Bj 
reducing  the  results  to  the  same  unit  of  weight,  it  nmy  be  .-ecn 
that  man  is  from  1000  to  1500  times  more  sensitive  to  this  remedy 
than  the  guinea-pig.  Therefore,  the  action  of  tuberculin  should 
be  studied  upon  man.  Koch  had  the  courage  to  experimenl  upon 
himself.  He  injected  0.25  c.cm.  of  the  "lymph"  into  his  arm. 
Three  or  four  hours  later  he  experienced  twitchings  in  his  limbs 
and  paroxysms  of  coughing;  later  on,  chills,  nausea,  vomiting,  and 
fever  attaining  102.2°  F.  (39°  C).  At  the  end  of  twelve  hours 
the  morbid  phenomena  disappeared,  except  a  slight  tired  feeling. 

In  a  healthy  man  or  in  individuals  suffering  from  a  non-tubercular 
affection,  it  is  necessary  to  employ  at  least  0.01  c.cm.  of  lymph  in 
order  to  produce  disturbances.  The  temperature,  rises  to  100.4°  F. 
(38°  C).  In  tuberculous  subjects  0.003  c.cm.  and  even  0.002  c.cm. 
suffices  to  arouse  intense  reactions. 

In  his  first  communication  Koch  reports  an  experiment  which 
seems  to  have  been  the  point  of  departure  of  his  investigations.  He 
asserted,  contrary  to  Dr.  Arloing,  that,  in  a  tubercular  guinea-pig, 
a  reinoculation  of  the  virus  gives  rise  to  only  slight  lesions  without 
any  tendency  to  generalization.  It  would  be  inferred  from  this  fact 
that  a  first  inoculation  confers  a  certain  degree  of  immunity.  Hence 
it  was  natural  to  investigate  whether  the  soluble  products  of  the 
tubercle  bacillus,  like  those  of  a  great  number  of  bacteria,  would  not 
act  in  the  same  manner.  Koch  claimed  to  have  obtained  this  result, 
but  he  indicated  it  only  incidentally  without  relating  any  experiment. 
Arloing,  Rodet,  and  Courmont  took  up  the  question.  They  pursued 
a  great  number  of  researches  on  this  subject  and  constantly  failed. 
The  animals  were  never  rendered  immune:  on  the  contrary,  at  times 
they  manifested  a  morbid  receptivity  and  succumbed  more  rapidly 

44 


690  INFECTIOUS  DISEASES. 

than  the  controls.  The  same  failure  attended  the  experiments  of 
Jaccoud,  Dujardin-Beaumetz,  and  Dubief.  It  may,  therefore,  be 
said  that,  with  respect  to  this  second  point,  Koch's  tuberculin  failed 
to  realize  what  had  been  promised  by  its  inventor. 

The  question  of  greater  consequence  is,  however,  the  therapeutic 
action  of  the  lymph.  In  this  regard,  Koch  teaches  us  that  small 
amounts  of  the  lymph  are  capable  of  killing  tubercular  guinea-pigs, 
while,  by  diminishing  the  doses,  it  is  possible  to  cause  reactions 
followed  by  a  notable  amelioration.  Are  the  guinea-pigs  cured,  how- 
ever? How  long  do  they  survive?  What  happens  as  a  result  of 
these  injections?  May  not  these  injections  cause  grave  and  tardily 
supervening  accidents,  as  the  experiments  of  Maffucci  tend  to  show? 
These  are  questions  requiring  answers.  Such  information  is  indis- 
pensable before  the  application  to  man  of  a  remedy  so  active  and 
so  dangerous. 

According  to  Koch,  the  lymph  is  to  be  used  for  therapeutic  pur- 
poses in  the  following  manner:  In  cases  of  pulmonary  tuberculosis 
very  small  doses  should  be  injected  at  first;  in  fortunate  cases  amel- 
ioration is  rapidly  produced.  Cough  diminishes,  the  expectoration 
assumes  a  mucous  character,  the  general  state  is  improved,  the 
bacilli  decrease  and  finally  disappear.  This  result  may  be  obtained 
in  four  or  six  weeks,  at  least,  in  patients  suffering  from  the  first  stage 
of  the  disease.  According  to  Koch,  such  patients  can  certainly  be 
cured.  Even,  however,  when  the  disease  has  reached  the  stage  of 
excavation  and  the  lung  is  invaded  by  innumerable  pyogenic  mi- 
crobes, the  treatment  may  still  produce  some  amelioration. 

By  studying  more  closely  the  modifications  occurring  in  tubercular 
foci  it  may  be  seen  that  the  lymph  acts  upon  the  tissues,  provided 
the  latter  be  yet  living  and  impregnated  with  toxin.  The  bacilli  are 
not  reached  and  are  simply  rejected  with  the  neighboring  parts. 
Be  that  as  it  may,  the  chief  action  of  the  lymph  is  upon  the  tissues 
surrounding  the  tubercles,  and  the  mechanism  of  this  action  was 
demonstrated  by  Bouchard's  experiments.  This  author  found  that 
tuberculin  acts  by  exciting  the  vasodilator  centre.  If  the  fundus  of 
the  eye  of  the  rabbit,  into  which  this  substance  has  been  injected, 
is  examined  an  active  dilatation  of  the  vessels  is  observed  (hence  the 
name  ectasin,  given  by  Bouchard  to  the  lymph).  This  dilatation 
persists  for  several  hours.  If,  however,  a  vasoconstrictor  substance 
or  anectasin  (for  example,  the  sterilized  culture  of  the  bacillus  pyo- 
cyaneus)  be  injected  into  a  rabbit  thus  prepared  the  papilla  becomes 


THEEAPEUTIOB  OF  INFECTIOUS  DI8EA8E8.  *;!>) 

anemic;  then,  at  the  end  of  half  an  hour,  the  action  of  the  anectasin 
having  ceased,  that  of  ecta  in  i  again  manifested  and  th< 
dilate.  The  same  phenomena  occur  around  those  tubercular  foci 
which,  in  consequence  of  the  vb  omotor  dilatation,  are  the  seal  of  a 
profuse  exudation  of  serosity  and  of  an  active  diapedesis  (Kromi 
Cornil).  The  neoplastic  tissue  re  i  I  .  or  it  i  econdarily  affected 
(coagulation  necrosis,  suppuration,  fatty  degeneration)  and  mi 
eliminated.  In  the  case  of  an  ulceration  occupying  a  mucous  mem- 
brane, it  becomes  I  ransformed  into  a  simple  wound  and  covered  with 
granulations  of  a  benign  nature  (Jurgens).  Moreover,  Koch  has 
remarked  that  successive  injections  arouse  le  and  I'  violent  reac- 
tions. In  his  opinion  this  result  is  not  due  to  the  formation  of  habit, 
but  to  the  progressive  disappearance  of  diseased  tissues.  When  all 
the  neoplasms  are  eliminated,  reaction  becomes  similar  to  thai  which 
is  presented  by  a  healthy  individual.  Lei  us  note,  however,  thai  in 
certain  oases  the  sensitiveness  of  the  patient  increases  with  each  new 
inoculation.  In  other  instances,  habil  is  established  long  before  the 
elimination  of  the  diseased  parts. 

Before  considering  the  results  obtained  by  various  physicians  who 
have  experimented  with  tuberculin,  we  must  briefly  indicate  the 
principal  dangers  to  which  this  medicine  exposes  the  subjects. 

These  dangers  are  at  times  dependent  upon  a  general  intoxication  : 
at  times  upon  a  too  intense  local  reaction.  Thus,  as  regards  the 
respiratory  apparatus,  pulmonary  edema  and  edema  of  the  glottis 
(which  has  in  some  cases  proved  fatal  by  suffocation),  hemoptysis, 
pleural  effusions,  and  bronchopneumonias  have  been  observed.  In 
other  cases  auscultation  has  revealed  an  aggravation  of  the  physical 
signs  connected  with  the  pulmonary  lesions,  which  have  sometimes 
caused  death.  Virchow  has  dwelt  upon  these  lesions,  which  he  desig- 
nated as  " injection  pneumonia,"  and  which  consist  essentially  of  a 
phlegmonous  process  which  causes  rapid  destruction  resulting  in  pul- 
monary excavations.  Coincident  ly,  new  small  tubercles  appear, 
which  are  due  to  a  "mobilization"  of  the  bacilli.  A  more  or  less 
torpid  tuberculosis  may  thus  rapidly  terminate  by  generalization  of 
the  infection  and  development  of  an  acute  miliary  tuberculosis. 
Experimenters  who  have  studied  the  action  of  therapeutic  doses  of 
the  lymph  in  tubercular  guinea-pigs  have  often  observed  similar 
effects.  In  this  connection,  nothing  is  more  instructive  than  the 
researches  of  Arloing  and  his  collaborators.  The  lymph  hastened 
generalization,   and  at  times  it  caused  this  condition   in  animals 


692  INFECTIOUS  DISEASES. 

inoculated  with  an  attenuated  virus  which  produced  only  local 
lesions. 

Intense  visceral  congestions  are  found  at  the  necropsy  of  animals 
killed  by  tuberculin  injections.  The  same  phenomena  are  observed 
in  man.  Thus,  there  are  on  record  hemorrhagic  nephrites,  renal 
congestions,  expressed  by  albuminuria  or  hematuria,  In  a  case  of 
Rosenbach's  the  patient  suffered  from  an  almost  complete  anuria; 
in  twenty-four  hours  he  voided  50  c.cm.  of  urine  of  a  mahogany 
color,  which  was  transformed  into  a  solid  mass  by  the  addition  of 
nitric  acid.  In  children  suffering  from  tubercular  meningitis  the 
use  of  the  tymph  gave  rise  to  acute  edema  of  the  meninges,  which 
hastened  the  fatal  termination.  Lastly,  under  the  influence  of  this 
medicine,  intestinal  ulcerations  have  been  seen  to  end  in  perfora- 
tion. 

Among  the  manifestations  ascribable  to  a  general  intoxication 
some  are  devoid  of  gravity.  Such  are  various  eruptions,  leucocy- 
tosis,  albuminuria,  urobilinuria  (Cavallero),  and  peptonuria;  the  last 
symptom  is  surely  due  to  the  medicine  itself,  since  it  has  been 
observed  in  healthy  individuals  (Kahler),  or  in  normal  animals 
(Bouchard).  In  other  cases  the  phenomena  are  more  serious.  Tran- 
sitory delirium  or  even  permanent  psychoses  occur  (Jolly).  Angina 
pectoris,  loss  of  consciousness,  coma,  and,  finally,  a  tendency  to  cardiac 
collapse  with  cyanosis,  cold  extremities,  weak  and  irregular  pulse 
may  supervene.  Even  permanent  lesions  of  the  endocardium  may 
occur  (Hallopeau). 

The  remedy  is  well  borne  only  in  those  cases  in  which  the  altera- 
tions are  superficial  and  the  mortified  tissues  can  easily  be  eliminated. 
In  fact,  accidents  are  rarer  when  the  lymph  is  employed  against 
cutaneous  tuberculosis  or  tuberculosis  of  the  conjunctiva,  nose, 
mouth,  and  intestine.  Its  action  on  the  larynx  must  be  very  care- 
fully watched.  Finally,  as  regards  the  lungs,  it  may  be  employed 
only  when  the  lesions  are  not  far  advanced  or  when  the  cavities 
communicate  largely  with  the  bronchi.  It  is  well  to  remark  that  if 
the  diseased  tissues  cannot  be  eliminated  by  expectoration  no  favor- 
able results  can  ever  be  obtained.  In  cases  of  articular  tuberculosis 
Prof.  Cornil  observed  enormous  painful  swelling  in  the  diseased 
joints.  At  the  end  of  a  certain  period  of  time  these  manifestations 
improved,  but  there  was  no  amelioration  of  the  disease.  On  the  other 
hand,  good  results  were  obtained  in  a  few  cases  in  which  surgical 
intervention  was  resorted  to. 


THERAPEUTIOB  OF  INFECTIOUS  DI8EA8E8.  693 

Are  fche  dangers  accompanying  injection  of  the  lymph  compen- 
sated l>y  fche  benefits  derived  by  fche  patient?  At  present  this  que  - 
tion  can  be  answered  in  a  deci  ive  manner.  Even  in  external  tuber- 
culoses, amelioration,  when  any  has  occurred,  has  been  mostly  rela- 
tive and  transitory.  In  cases  of  lupus  /.  e.f  in  instance  in  which 
the  best  results  ;irc  obtained  -only  the  superficial  nodules  are  elim- 
inated; the  deep-seated  ones  persist,  and  the  patients  Boon  - 
to  present  any  more  reaction  al  the  diseased  point,  even  when 
doses  of  0.08  c.cm.  are  employed.  In  this  connection,  nothing  i-  ■■>- 
instructive  as  the  perusal  of  the  reporl  prepared  by  Dr.  Besnier 
in  the  name  of  the  St.  Louis  Hospital  Commission.  It  regards  the 
treatment  of  thirty-eight  cases  of  lupus.  Improvement  frequently 
occurred,  especially  in  the  open  forms  of  the  disease,  bu1  this  im- 
provement was  not  permanent,  and  the  affection  resumed  its  course. 
At  times  it  was  aggravated.  Thus,  even  in  cases  of  attenuated  tuber- 
culoses, Koch's  treatment  is  often  inefficient.  In  other  cases  it  may 
prove  dangerous.  The  use  of  the  lymph  was  therefore  gradually 
abandoned. 

It  would,  however,  be  unjust  to  wholly  condemn  the  method. 
Although  tuberculin,  taken  as  a  whole,  is  more  harmful  than  other- 
wise, it  may  be  hoped  that  it  will  some  day  be  possible  to  separate 
the  curative  substances  contained  in  it.  This  is  what  Koch,  with  the 
assistance  of  Proskauer  and  Brieger,  has  attempted.  The  substance 
which  he  obtained,  however,  produces  the  same  dangerous  effect-  as 
the  raw  tuberculin,  and  is  no  more  to  be  recommended  than  the 
former.  W.  Hunter  announced  in  the  London  Congress  of  1895  that 
he  had  isolated  from  tuberculin  three  active  substances:  the  first 
one,  of  an  albuminoid  nature,  is  hyperthermizing :  the  other  two  are 
albumoses,  one  of  which  possesses  a  phlogogenic  power,  the  other 
exerts  a  curative  action.  Klebs,  Kuhne,  and  Rohmer  have  pur- 
sued similar  researches. 

In  a  more  recent  communication  Koch  indicated  a  new  prepara- 
tion of  tuberculin:  The  desiccated  bacilli  are  triturated  in  an  agate 
mortar  with  a  pestle  of  the  same  substance.  The  magma  is  taken 
with  a  little  water  and  is  centrifuged  for  thirty  to  thirty-five  minutes. 
The  fluid  obtained  is  tuberculin  0,  which  is  analogous  to  the  old  raw 
tuberculin.  It  possesses  no  therapeutic  properties.  The  residue  is 
then  taken,  dried,  and  again  triturated,  and.  after  having  added  water 
to  it,  is  again  centrifuged.  When  this  operation  has  been  repeated 
several  times  almost  all  the  precipitate  is  exhausted  and  a  series  of 


694  INFECTIOUS  DISEASES. 

fluids  obtained  which  are  mixed  together.  Thus  is  obtained  tuber- 
culin R,  which,  unlike  tuberculin  0,  contains  substances  insoluble  in 
glycerin.  This  new  tuberculin  is  germicidal,  it  causes  no  abscesses, 
and  possesses  immunizing  and  curative  properties.  No  febrile  reac- 
tion is  said  to  occur.1 

The  first  control  researches  due  to  Letulle  and  Peron2  have  hardly 
been  favorable  to  the  method.  Its  only  advantage  is  that  it  is  not 
dangerous.3  Judging,  however,  by  the  small  number  of  facts  thus 
far  published,  it  does  not  seem  that  we  as  yet  possess  the  specific 
remedy  of  tuberculosis. 

Mallein.  The  discovery  of  tuberculin  led  bacteriologists  to  look 
for  analogous  substances  in  other  cultures.  Thus,  Helman  and 
Kalning  prepared  a  substance,  mallein.  This  product  is  hardly  ever 
used  for  any  other  than  diagnostic  purposes.  According  to  Bonome 
and  Vivaldi,  even  minute  doses  cause  death  in  cats  suffering  from 
glanders,  while  they  produce  amelioration  in  guinea-pigs,  rabbits, 
and  man.  As  to  the  horse,  numerous  experiments  seem  to  demon- 
strate that  mallein  may  favor  cicatrization  and  at  times  bring  about 
a  recovery,  at  least  when  the  lesions  are  recent  and  discrete. 

A  last  attempt  was  made  with  reference  to  typhoid  fever.  E. 
Fraenkel  treated  patients  with  sterilized  cultures  of  Eberth's  bacillus. 
The  first  effect  is  a  rise  in  the  temperature,  followed  by  an  at  least 
temporary  fall.  The  statistics  published  by  the  author  seem  quite 
encouraging. 

Serumtherapy. 

The  discovery  of  serumtherapy,  the  way  to  which  was  prepared 
by  the  researches  on  the  germicidal  properties  of  the  fluids  of  the 
organism  and  by  the  efforts  of  experimental  therapeutics,  due  to 
Drs.  Richet  and  Hericourt,  belongs,  as  is  known,  to  Behring  and 
Kitasato.  Having  recognized  that  the  serum  of  animals  vaccinated 
against  diphtheria  is  antitoxic  they  were  led  to  employ  it  for  thera- 
peutic purposes. 

After  the  data  reported  in  the  preceding  chapter  we  may  readily 
comprehend  the  radical  difference  separating  bacteriotherapy  from 

1  Koch.  Ueber  neue  Tuberkulin  Praeparate.  Deutsche  med.  Wochenschrift,  August 
1,  1897. 

2  Letulle  and  Peron.  La  nouvelle  tuberculine  de  Koch.  La  presse  m^dicale,  August 
21,  1897. 

3  Borquier.  La  nouvelle  tuberculine  R  et  son  emploi,  en  particulier  dans  la  tuber- 
culose  pulmonaire.     Th6.se  de  Paris,  1897. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

serumtherapy.  The  aim  of  the  former  method  i  to  acl  with  the 
products  secreted  by  microbes,  that  of  the  second  i  to  di  cover  in 
the  blood  not  what  remains  of  the  toxins  introduced,  but  the  prin- 
ciples which  are  developed    under  its   influence.     Serumtherapy 

employs  materials  elaborated  by  the  organism  itself  in  r 
against  infection.  It  is  therapeutic  and  vaccinating  alike,  bul  the 
immunity  which  it  confers  is  a  passive  immunity.  The  organism 
takes  no  part  in  its  production;  if  makes  no  effort :  it  simply  allows 
itself  to  be  impregnated  by  the  substances  introduced.  On  the  other 
hand,  bactcriotherapy  is  ol'lener  preventive  than  curative.  It  pro- 
duces immunity,  but  by  means  of  an  altogether  different  mechanism. 
It  is  a  process  of  active  immunity  dependent  upon  an  efforl  of  the 
organism. 

Choice  of  the  Animal.  It  was  formerly  believed  thai  the  more 
sensitive  the  organism  was  to  the  disease  the  better  it  reacted.  This 
idea,  led  authors  to  vaccinate  the  most  susceptible  animals.  At  pres- 
ent it  seems  to  be  demonstrated  lhat,  although  the  law  is  real,  it  is 
subject  to  numerous  exceptions  and  that  it  is  possible  to  confer  active 
immunity  whether  the  animals  are  naturally  refractory  or  not.  We 
have  proof  of  this  in  what  occurs  in  diphtheria.  Behring  believed 
that  an  animal  sensitive  to  the  virus  should  be  employed,  and  he 
experimented  upon  sheep.  Roux  has  shown  that  the  horse,  which 
is  only  slightly  susceptible  to  diphtheria,  gives  just  as  efficacious  a 
serum.  The  same  is  true  of  tetanus;  Roux  and  Vaillard  have  demon- 
strated that  the  chicken,  which  does  not  contract  this  infection,  fur- 
nishes a  therapeutic  serum  when  large  amounts  of  toxins  are  injected 
into  it. 

It  is  not  so  much  the  degree  of  sensitiveness  or  natural  resistance 
of  the  animal  as  the  possibility^  of  easily  obtaining  large  quantities 
of  blood  and  a  serum  devoid  of  toxic  properties  that  must  guide  us 
in  our  choice.  In  fact,  it  is  known  that  transfusion  between  indi- 
viduals of  different  species  is  not  always  inoffensive.  Experimenta- 
tion cannot,  however,  furnish  decisive  data  to  therapeutics,  for  the 
toxicity  of  the  serum  of  a  given  species  varies  considerably,  according 
to  the  species  into  which  it  is  injected.  It  is,  therefore,  impossible 
to  know  with  sufficient  accuracy  what  its  effect  would  be  in  man. 
Nevertheless,  it  is  interesting  to  look  for  the  solution  of  the  problem 
in  animals. 

By  making  intravenous  injections  of  various  serums  into  rabbits, 
the  following  results  have  been  obtained : 


696  IXFECTIO  US  DISEASES. 

Animal  Furnishing  the  Serum.  Fatal  Dose  for  One  Kilogram  of  Babbit. 

Cattle 8  c.em.  (Runimo  and  Bordoni). 

Sheep 12  c.em.  (Runimo  and  Bordoni). 

Calf 13  c.em.  (Runimo  and  Bordoni). 

Man 15  c.em.  (Mairet  and  Bosc). 

Chicken 20  c.em.  (Runimo  and  Bordoni). 

Horse 80  c.em.  (Zagari). 

Clinical  facts  seem  to  be  in  harmony  with  the  data  of  experimen- 
tation for  establishing  that  the  serum  of  the  dog  is  not  well  borne, 
while  that  of  the  horse  is  excellent,  and  may  be  employed  in  large 
doses.  The  serum  of  the  cow,  which  is  very  toxic  for  the  rabbit,  is 
very  slightly  so  for  man.  In  the  treatment  of  variola  Dr.  Beclere 
injected  as  much  as  1560  c.em.  without  giving  rise  to  any  disturbance. 
Finally,  it  is  certain  that  the  serum  of  man  would  be  the  best  from 
this  standpoint.  It  will  be  shown  later  on  that  it  has  been  employed 
in  therapeutics  in  exceptional  cases. 

Vaccination  of  Animals.  The  animal  being  chosen,  the  reactions 
of  its  organism  must  be  called  into  play  in  order  to  increase  its 
resistance.    This  may  be  realized  by  three  methods: 

1.  Inoculation  of  living  microbes. 

2.  Injection  of  toxins  produced  in  artificial  cultures. 

3.  Injection  of  toxins  derived  from  the  diseased  organism. 

The  first  procedure  exposes  to  certain  accidents.  After  injection 
of  living  cultures  into  animals  the  microbes  may  persist  in  the  blood, 
even  when  the  subject  seems  to  have  recovered.  For  instance,  the 
antistreptococcic  serum  derived  from  animals  prepared  by  means  of 
living  cultures  has  sometimes  caused  phlegmonous  erysipelas,  be- 
cause it  still  contained  streptococci  which  were  undoubtedly  atten- 
uated, but  nevertheless  capable  of  producing  local  lesions. 

Of  course,  this  danger  may  be  avoided  by  employing  sterilized  cul- 
tures, modified  or  not  by  physical  or  chemical  agents.  There  is  no 
doubt  that  immunity  thus  created  is  much  less  durable  than  when 
it  results  from  virulent  inoculations.  However,  it  then  suffices  to 
repeat  the  injections  of  toxins  for  maintaining  or  increasing  the 
properties  of  the  serum,  for  it  is  to  be  noted  in  this  connection  that 
repeated  injections  of  small  doses  are  more  efficient  than  the  intro- 
duction of  a  single,  even  though  greater,  amount  (Roux  and  Metch- 
nikoff). 

The  animals  vaccinated  by  means  of  soluble  substances  have 
already  been  employed  for  the  preparation  of  a  great  number  of 
serums.     It  is  quite  evident  that  serums  may  be  obtained  against 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  897 

all  the  known  pathogenic  agents,  on  condition,  however,  thai  B 
method  of  vaccination  can  be  found.  For  example,  the  rea  on 
attempts  failed  in  tuberculosis  is  thai  it  ha  ao1  yel  been  po  ible 
to  confer  upon  animals  a  genuine  immunity  againsl  thij  infection. 

The  serumtherapy  method  may  be  employed  even  when  the  path- 
ogenic agent  has  not  been  isolated.  Under  the  e  condition  ,u  emay 
be  made  according  to  the  requirements  of  the  ca  e  of  one  of  the 
following  procedures: 

The  serum  from  animals  vaccinated  by  meant  of  more  or  less  modi- 
fied virulent  tissue.  This  is  done,  for  instance,  in  regard  to  hydro- 
phobia. 

The  blood  obtained  after  t  he  cure  of  the  disease,  whether  the  latter 
be  spontaneous  or  inoculated.  For  diseases  which  are  nol  transmis- 
sible to  animals,  man  is  experimented  upon.  After  hie  recovery 
blood  is  taken  from  him  which  is  employed  for  reinforcing  the  n 
ance  of  patients.  This  has  been  done  notably  in  typhus  fever,  scar- 
latina, and  rheumatism. 

Lastly,  in  the  case  of  a  non-inoculable  disease,  fluids  or  extracts 
of  tissues  may  be  taken  and  injected  into  animals  so  as  to  arouse 
reactions  on  the  part  of  the  organism.  This  method,  which  is  highly 
rational,  has  not  yet  received  many  applications. 

It  is  likewise  possible  to  employ  extracts  taken  from  organs  in 
which  the  toxic  substances  accumulate  or  are  produced.  Drs.  Heri- 
court  and  Richet  have  resorted  to  this  procedure  to  prepare  an  anti- 
neoplastic serum. 

These  various  procedures  render  the  serum  efficacious  because  they 
increase  the  resistance  of  the  animal.  This  is  demonstrated  when 
the  disease  is  inoculable,  and  this  is  assumed  to  be  true  when  the 
disease  is  not  inoculable. 

This  brief  exposition  suffices  to  show  how  numerous  are  the 
possible  applications  of  serumtherapy.  There  is  hardly  a  disease 
against  which  a  serum  cannot  be  prepared.  Theoretically,  the  prob- 
lems are  easily  solved  while,  as  w*e  shall  see  later,  practical  applica- 
tions have  not  completely  realized  the  hopes  which  were  aroused  by 
laboratory  researches.  The  more  we  study  the  question  the  greater 
we  find  the  difficulties  to  be  overcome. 

Various  Organic  Fluids  Employed  in  Therapeutics.  Therapeutic 
action  being  dependent  upon  soluble  substances,  serum  as  well  as 
defibrinated  blood  may  be  used  indifferently.  As  the  latter  product 
is  more  difficult  of  manipulation,  the  former  is  generally  resorted  to. 


098  IMECTIOUS  DISEASES. 

Delbet,  however,  has  thought  it  advantageous  to  utilize  the  total  blood 
just  as  it  is  obtained,  when  coagulation  is  prevented  by  means  of  an 
oxalate  which  precipitates  the  calcium  salts.  Nothing  is  easier  than 
tin'  preparation  of  serums.  Two  or  three  quarts  (litres)  of  blood  are 
taken  from  the  jugular  of  a  horse.  The  clot  that  forms  is  very  solid, 
and  the  serum  has  a  fine  yellow  amber  color.  It  is  kept  in  sterilized 
small  vials,  containing  a  few  drops  of  some  antiseptic  oil  or  a  little 
sublimated  camphor.  One  of  the  inconveniences  of  the  method  is 
that  successive  blood-letting,  especially  when  repeated  at  short  inter- 
vals, often  weakens  the  therapeutic  action  of  the  serum.  This  we 
have  shown  to  be  true  at  least  as  regards  the  antistreptococcic  serum, 
and  Marchoux  has  made  the  same  observation.  It  has,  therefore, 
been  believed  that  it  was  possible  to  replace  the  blood  by  a  fluid 
more  easily  procurable — milk,  for  example.  The  experiments  of 
Brieger,  Ehrlich,  and  Ketscher  have  established  that  this  fluid  pos- 
sesses therapeutic  properties,  but  it  is  ten  times  less  active  than 
serum,  hence  it  cannot  be  used  except  when  it  is  previously  concen- 
trated. 

The  curative  fluid  is  generally  introduced  beneath  the  skin.  Intra- 
venous injection  is  employed  only  in  laboratories.  Introduction  by 
the  digestive  canal  does  not  seem  highly  reliable.  Ehrlich  demon- 
strated that  the  therapeutic  substances  present  in  the  milk  may 
impregnate  the  organisms  of  the  }roung  who  ingest  it,  but  this  result 
is  observed  only  in  nursing  animals.  In  fact,  Ketscher  has  shown 
that  the  milk  of  goats  immunized  against  cholera  is  curative  when 
injected  beneath  the  skin,  but  produces  no  effect  when  it  is  ingested. 
The  active  substance  seems  to  be  destroyed  by  the  pepsin  and  pan- 
creatic juice  during  digestion.  When  it  is  desired  to  introduce  the 
serum  by  the  alimentary  canal  it  should,  according  to  the  advice  of 
Dr.  Chantemesse,  be  given  in  the  form  of  enemata. 

It  is  not  necessary  to  dwell  upon  the  rules  of  subcutaneous  injec- 
tions of  serum.  Except  in  certain  special  cases,  the  injection  may 
be  made  into  any  part  of  the  body.  When,  however,  considerable 
quantities  are  to  be  introduced,  it  is  advisable  to  operate  upon  the 
abdominal  region.  Here  the  fluid  is  better  tolerated  and  most  rapidly 
absorbed.  The  dose  to  be  injected  varies  evidently  according  to  the 
gravity  of  the  case  and  the  activity  of  the  serum.  The  former  factor 
can  be  appreciated  by  clinical  observation  alone;  the  latter  may  be 
determined  with  accuracy.  Hence,  from  the  very  beginning  of  his 
researches,  Behring  endeavored  to  determine  an  exact  measure  for 


THERAPEUTICS  OF  INFECTIOUS  DISEASE8.  699 

the  activity  of  serum.    He  firs!  took  ass  unit  the  quantity  oi  scrum 

which  insured  against  the  smallest  fatal  dose  of  the  toxin.  ll< 
adopted,  however,  the  method  proposed  by  Ehrlich.  Thu  if  prac- 
tised in  the  following  manner:  The  minimum  fatal  do  e  a  regards 
the  guinea-pig  is  determined,  and  then  an  amount  of  toxins  equiva- 
lent to  ten  fatal  doses  is  employed.  This  amount  of  toxin  is  called 
by  Behring  the  toxin  unit.  This  unit  is  then  mixed  with  serum, and 
the  whole  is  injected  beneath  the  skin  of  guinea  pigs.  Normal  anti- 
toxin is  of  such  strength  that  0.1  c.cm.  neutralizes  the  toxin  unit 
i.  c,  ten  times  the  fatal  dose  Behring  called  an  antitoxin  unit  the 
amount  of  antitoxin  contained  in  I  c.cm.,  and,  consequently,  capable 
of  neutralizing  ten  toxin  units  or  one  hundred  times  the  fatal  dose. 
When  it  is  said  that  a  serum  has  the  value  of  ten  units  this  means 
that  1  c.cm.  neutralizes  one  hundred  toxin  units  or  one  thousand  fatal 
doses,  or  that  the  toxin  unit  is  neutralized  by  0.01  c.cm.  A  serum 
presenting  one  hundred  units  is  of  such  potency  that  1  c.cm.  neu- 
tralizes one  thousand  toxin  units  or  ten  thousand  fatal  doses,  and  BO 
on.  This  nomenclature  is  generally  employed,  except  in  the  Pasteur 
Institute,  where  the  preventive  power  and  not  the  antitoxic  action 
is  determined.  The  animal  which  is  to  serve  for  the  determination 
receives  the  serum,  and  the  following  day  the  minimum  fatal  dose 
is  inoculated  into  it.  The  unit  is  the  number  of  grams  which  1  c.cm. 
of  serum  is  capable  of  protecting.  If,  for  example,  a  guinea-pig 
weighing  400  grams  is  preserved  by  0.008  c.cm.  of  serum,  0.02  c.cm. 
would  be  required  for  1000  grams.  Therefore,  1  c.cm.  would  preserve 
50,000  grams  of  the  animal.  Hence,  it  is  said  that  the  serum  has 
the  power  of  50,000.  Such  is  the  unit  of  serum  furnished  by  the 
Pasteur  Institute.  This  method  is  not  without  advantage,  but  it 
presents  a  great  inconvenience,  for  in  employing  the  smallest  fatal 
dose  one  may,  perchance,  experiment  upon  an  animal  endowed  with 
a  certain  resistance,  and  attribute  to  the  serum  what  is  really  due  to 
the  particular  state  of  the  animal.  This  source  of  error  is  avoided 
when  the  experiment  is  made  with  an  amount  of  toxin  ten  times 
larger  than  the  minimum  fatal  dose. 

The  method  of  mixture  is  applicable  not  only  to  toxi-infectious 
diseases,  such  as  diphtheria  and  tetanus,  but  it  may  also  be  used  to 
determine  the  action  of  a  serum  upon  a  living  culture.  It  is  well  to 
note,  however,  that  in  the  latter  case  the  results  are  very  different, 
according  as  a  mixture  of  serum  and  microbes  is  injected  or  according 
as  the  serum  and  the  culture  are  introduced  at  two  different  points 


700  IXFECTIO  US  DISEASES. 

or  successively  at  one  and  the  same  point.  The  curative  action  is 
far  more  marked  when  the  serum  and  microbes  come  in  contact. 

Various  Applications  of  Serumtherapy.  The  works  to  which 
the  serumtherapy  method  has  given  rise  are  so  numerous  that  it  is 
impossible  to  present  here  a  complete  summary  of  them.1  The  dis- 
eases which  may  be  treated  by  this  method  are  divided  into  two 
groups  according  as  the  pathogenic  agent  is  or  is  not  known  and 
cultivable. 

The  following  is  a  list  of  infectious  diseases  for  the  treatment  of 
which  serumtherapy  has  been  practised: 

Anthrax.  Measles. 

Cholera.  Scarlatina. 

Colon  bacillosis.  Staphylococcosis. 

Diphtheria.  Streptococcosis. 

Leprosy.  Syphilis. 

Glanders.  Tetanus. 

Bubonic  plague.  Tuberculosis. 

Pneumococcosis.  Typhoid  fever. 

Proteobacillosis.  Typhus  fever. 

Pyocyanobacillosis.  Recurrent  typhus. 

Hydrophobia.  Vaccinia  and  variola. 
Rheumatism. 

If  we  wish  to  make  a  complete  study  of  serumtherapy  we  should 
add  the  diseases  peculiar  to  animals,  such  as  symptomatic  anthrax, 
certain  hemorrhagic  septicemias,  the  disease  of  dogs,  murr,  and  in- 
toxications, notably  poisonings  by  toxalbumins  and  venoms. 

Cholera.  Cholera  has  been  the  subject  of  important  serum- 
therapic  experiments,  and  the  results  obtained,  besides  their  theo- 
retic interest,  seem  to  be  of  such  a  character  as  to  lead  us  to  hope 
that  they  will  be  applied  to  human  therapeutics  in  the  near  future. 

In  1892  Lazarus  showed  that  a  decigram  of  the  serum  of  indi- 
viduals cured  of  cholera  is  capable  of  protecting  the  guinea-pig 
against  an  intraperitoneal  inoculation  of  cholera  vibrios.  This 
result,  confirmed  by  various  experimenters,  was  highly  important. 
It  was  objected,  however,  that  the  serum  of  normal  men  and  animals 
often  possesses  immunizing  and  curative  properties.  The  result 
being  uncertain,  it  was  necessary  to  investigate  what  occurs  as  a 
result  of  vaccination.  As  early  as  1890  Zasslein  demonstrated 
that,   under   these   conditions,   the   serum   acquires   very  marked 

1  A  complete  description  of  serumtherapy  and  the  principal  bibliographical  indications 
may  be  found  in  the  report  which  the  author  presented  to  the  Congres  franyais  de 
m^decine :  Des  applications  des  serums  sanguins  au  traitement  des  maladies.  Nancy, 
August  6,  1896.     Consult  also:  Landouzy,  Les  Serotherapies.     Paris,  1898. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  70] 

germicidal  properties,  and,  a  few  years  later,  Pawlowski  and  Buch- 
stab, taking  blood  from  vaccinated  rabbits  and  guinea-pigs,*  ucceeded 
in  conferring  immunity  upon  animals  of  the  same    pecie        l 
results  were  confirmed  by  Pfeiffer  and  [ssaeff,  and  became  the  point 
of  departure  for  a  scries  of  very  Lmportanl   research*  rting 

from  the  principle  that  the  cholera  toxin  is  contained  in  the  vibrio* 
and  is  not  liberated  until  after  the  latter  are  disintegrated,  Pfeiffer 
was  led  to  immunize  animals  by  injecting  into  them  culture*  steril- 
ized by  heat  or  chloroform  vapor  or  by  inoculating  into  them  pro- 
gressive doses  of  living  vibrios.  By  these  procedures  he  succeeded 
in  obtaining-  a  serum  of  extraordinary  efficiency,  bul  one  which 
does  not  act  except  against  vibrionic  peritonitis.  It  fails  when  it 
is  applied  to  animals  inoculated  by  way  of  the  intestine.  The  result 
which,  from  a  theoretical  standpoint,  was  of  considerable  impor- 
tance, did  not  lead  to  any  practical  application.  Jt  was,  therefore, 
necessary  to  take  up  the  question  under  inspiration  of  the  principles 
which  had  guided  Behring.  This  was  done  by  his  disciple  Ramson. 
In  speaking  of  the  mechanism  of  immunity,  we  have  already  referred 
(p.  564)  to  the  result  obtained  by  this  author  with  an  antitoxic 
serum  quite  different  from  the  antibacterial  serum  obtained  by 
Pfeiffer. 

Metchnikoff,  Roux  and  Taurelli-Salimbeni  have  prepared  a  very 
active  antitoxic  serum;  54  per  cent,  of  the  animals  treated  with  this 
fluid  survived,  and  16  per  cent,  of  the  controls. 

These  highly  interesting  results  thus  open  the  field  for  therapeutic 
application.  Of  course,  the  phenomena  are  always  more  complex 
in  man,  in  whom  we  must  take  cognizance  of  microbic  associations 
which  seem  to  play  such  a  considerable  role  in  the  pathogenesis 
of  cholera.  It  must  also  be  demonstrated  that  the  serum  obtained 
by  vaccinating  an  animal  against  one  vibrio  acts  upon  all  varieties 
of  the  colon  bacillus.  Even  leaving  aside  the  vibrios,  which  seem 
to  represent  species  or  at  least  fixed  races,  like  the  bacillus  of  Finkler- 
Prior  and  the  avicidal  vibrio  of  Gamaleia.  it  is  known  that,  in 
various  cholera  epidemics,  quite  different  microbes  have  been  found. 
Such,  for  instance,  are  the  bacilli  of  Massouah,  Ghinda,  and  Ham- 
bourg.  On  the  other  hand,  Pfeiffer  has  shown  that  the  serum  of 
an  animal  immunized  against  one  variety  of  microbe  does  not  act 
upon  the  others.  This  fact  is  so  constant  that  the  author  considers 
it  a  means  of  diagnosticating  different  bacilli.  It  is  true  that  these 
results,  which  have  not  been  completely  confirmed  by  Sanarelli. 


702  INFECTIOUS  DISEASES. 

have  been  obtained  in  studying  vibrional  peritonitis  and  the  serum 
which  acts  upon  the  figurate  element.  The  toxin  is  probably  always 
the  same,  and  the  antitoxic  serum  may  succeed  in  all  cases.  This 
question  is  worthy  of  study. 

Even  before  the  recent  researches  on  antitoxins,  a  few  attempts 
were  made  upon  man.  During  the  epidemic  of  Hamburg,  Freymouth 
investigated  the  effects  produced  by  the  serum  of  convalescents. 
Having  learned  that  half  a  cubic  centimetre  injected  into  the  peri- 
toneum of  a  guinea-pig  protects  it  against  an  inoculation  of  four- 
fifths  of  a  cubic  centimetre  of  virulent  culture,  he  practised  injec- 
tions upon  three  patients.  The  first  one  who  had  been  attacked  for 
forty-eight  hours  received  successively  10,  30,  and  50  c.cm.  a  day. 
The  patient  at  first  seemed  to  feel  better,  but  on  the  fifth  day  he 
grew  worse,  and  death  occurred  on  the  sixth  day.  The  second 
patient  recovered  after  an  injection  of  30  c.cm.  on  the  third  day. 
On  the  sixth  day,  however,  he  still  had  vomiting  and  rhiziform 
diarrhea.  The  third  case  was  that  of  a  woman  suffering  from  a 
slight  attack.  Her  symptoms  rapidly  improved  after  an  injection 
of  20  c.cm.  These  observations  are  too  few  in  number  to  warrant 
a  conclusion.  At  any  rate,  the  method  which  consists  in  injecting 
the  blood  of  convalescents  cannot  have  a  great  future.  Anticholeric 
serum  must  have  an  animal  origin,  and  recent  experiments  with 
choleric  antitoxins  seem  to  have  greatly  advanced  the  question. 
The  experimental  study  is  nearly  completed;  clinical  observation 
must  decide  the  problem. 

Colon  Bacillus.  As  the  colon  bacillus  constantly  secretes  toxic 
substances  in  the  intestine,  it  is  plain  that  a  series  of  reactionary 
phenomena  terminating  in  the  production  of  antitoxins  must  occur 
within  the  organism.  This  is  precisely  what  takes  place.  The  serum 
of  normal  individuals  may  neutralize  doses  of  B.  coli  ten  times 
larger  than  those  which  are  usually  fatal.  Thus  we  recognize  a 
first  spontaneous  effort  toward  immunization.  It  suggested  the 
next  step,  which  consists  in  increasing  the  resistance  of  the  organism 
by  the  usual  procedures.  Cesaris,  Demel  and  Orlandi,  Salvati  and 
Gaetano  demonstrated  that  the  soluble  products  of  the  colon 
bacillus  are  capable  of  conferring  immunity  upon  animals  and 
imparting  therapeutic  characters  to  their  sera. 

Drs.  Albarran  and  Mosny,  having  vaccinated  animals  by  alter- 
native injections  of  filtrates  of  the  organs  of  animals  dead  from 
colon  bacillosis  and  of  living  cultures,  obtained  a  serum  which,  in 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  70:; 

doses  of  0.().r>  c.cm.,  immunized  the  guinea  pig  again  I  a  srirulenl 
inoculation  practised  twenty-four  hours  later;  0.25  c.cm.  sufficed 
to  protect  against  an  amounl  twenty  time  larger  than  the  fatal 
dose.  By  studying  the  serum  according  to  the  method  of  mixture, 
it  may  be  seen  that  one  drop  neutralizes  the  fatal  dose.  Finally, 
2  c.cm.  injected  two  hours  after  inoculation  of  an  amount  of  culture 
equal  to  double  the  fatal  dose  saved  the  animal  1. 

These  results  are  sufficiently  encouraging  to  warrant  practical 
applications,  notably  in  urinary  infections,  which  Drs.  AJbarran  and 
Mosny  had  particularly  in  view.  It  is  more  difficult  to  employ  the 
serum  under  other  circumstances,  since  it  is  nol  alway  possible  to 
determine  during  the  life  of  animals  whether  the  symptoms  are  due 
to  the  colon  bacillus  or  not.  The  serum  cannot,  therefore,  be  utilized 
except  in  certain  surgical  cases. 

The  close  analogy  existing  between  the  colon  bacillus  and  the 
bacillus  of  Eberth  have  led  some  experimenters  to  invest  ig:it  e  whether 
the  serum  which  antagonizes  colon  bacillary  infection  can  likewise 
combat  typhoid  fever.  Sanarelli  demonstrated  the  mutual  immuni- 
zation by  the  two  bacilli.  C.  Dcmel  and  Orlandi  recognized  that  the 
serum  of  animals  vaccinated  against  the  colon  bacillus  prevents 
experimental  typhoid  infection.  They  have  even  made  attempt-  on 
man  and  obtained  improvement  by  treating  typhoid  cases  with  this 
serum. 

In  spite  of  their  interest,  these  results  should  not  be  considered 
as  proving  that  the  anticolon  bacillus  serum  is  the  specific  of  typhoid 
fever.  Loeffler  and  Abel  proved  that,  although  the  anticolon  bacillus 
serum  acts  upon  typhoid  infection  and  the  antityphoid  serum 
upon  colon  bacillus  infection,  each  of  the  sera  is  especially  active 
when  employed  in  the  treatment  of  the  disease  against  which  the 
animal  furnishing  the  serum  has  been  previously  protected.  Here 
is  a  question  of  specificity  which,  while  not  absolute,  is  nevertheless 
undeniable. 

Diphtheria.  The  employment  of  antidiphtheritic  serum  has  com- 
pletely transformed  the  prognosis  of  diphtheria.  All  statistics 
clearly  establish  that,  under  the  influence  of  the  new  medication, 
the  death-rate  has  diminished  in  extraordinary  proportions  and  the 
period  of  convalescence  considerably  reduced.  Moreover,  the  rapid 
evolution  of  the  disease  has  enabled  the  physician  to  abandon 
tracheotomy  and  to  substitute  intubation  for  this  operation.  It 
would  be  right  to  devote  the  greatest  part  of  this  chapter  to  the 


704  INFECTIOUS  DISEASES. 

study  of  the  antidiphtheritic  serum.  The  question  is  so  well  known 
to-day,  however,  that  we  shall  be  contented  with  a  summary  of  the 
most  important  facts. 

Science  is  indebted  to  Behring  for  the  two  discoveries  which  led 
to  the  preparation  of  the  serum.  He  demonstrated  the  certain 
means  of  immunizing  animals  against  diphtheria,  and  he  subse- 
quently recognized  that  then'  sera  became  antitoxic.  On  this  latter 
discovery  antidiphtheritic  serumtherapy  is  founded.  In  human 
therapeutics  he  employed  the  serum  of  sheep  immunized  by  means 
of  toxins  attenuated  by  trichloride  of  iodine.  Aronson  used  the 
serum  of  dogs.  He  later  employed  the  serum  of  the  horse.  Roux 
and  Martin  also  resorted  to  the  horse.  They  added  to  the  toxin 
one-tenth  of  its  volume  of  Gram's  fluid,  which  contains  1  gram 
of  iodine,  3  grams  of  potassium  iodide,  and  100  grams  of  water. 
One-fourth  of  a  cubic  centimetre  of  the  mixture  is  first  injected, 
and  the  dose  is  progressively  increased.  It  is  thus  possible  at  the 
end  of  three  months  of  treatment  to  reach  a  dose  of  250  c.cm.  of 
the  filtered  culture. 

The  first  therapeutic  applications  to  the  human  subject  were  made 
in  1892  in  the  wards  of  Dr.  Henoch,  in  Berlin.  They  were  not  very 
encouraging.  Two  years  later,  however,  a  new  series  of  contributions 
appeared  which  determined  conclusively  the  value  of  the  serum. 
Ehrlich,  Kossel,  and  Wassermann  first  reported  the  results  of  233 
inoculations  practised  upon  children.  The  death-rate  was  23  per 
cent.  In  a  great  number  of  cases  the  serum  employed  was  not  very 
active.  Truly  efficacious  serum  had  been  used  only  in  92  cases,  and 
the  death-rate  had  fallen  to  12  per  cent.  About  the  same  time 
Korte  presented  statistics  of  121  cases.  The  death-rate  was  33  per 
cent.,  while  previous  to  the  use  of  the  serum  it  was  45  per  cent. 
The  figures  of  Aronson  are  far  better.  With  his  antitoxin  he  had  a 
death-rate  of  12  per  cent,  in  a  total  of  255  diphtheritic  children. 

It  would  be  superfluous  to  recall  other  less  important  statistics1 
published  in  Germany  about  the  same  period,  indicating  a  notable 
decrease  in  the  death-rate.  The  results  obtained  in  France  are  by 
no  means  less  favorable.     In  a  very  remarkable  thesis  Bayeux2 

1  For  all  statistics  and  bibliographical  data  relative  to  this  first  period,  consult  the 
article  of  L6pine:  La  se>otherapie  de  la  diphterie.  Semaine  m^dicale,  1894,  p.  573. 
See  also  the  report  presented  by  Haushalter  in  the  Congres  de  Nancy,  August,  1896. 

2  Bayeux.  La  diphtdrie  depuis  Aret§e  le  Cappodocien.  R^sultats  statistiques  de 
230,000  cas.     Thfee  de  Paris,  1899. 


THERAPEUTICS  OF  INFECTIOUS  DI8EASE8.  70.", 

tabulated  all  the  statistics  and  reached  the  conclu  ion  thai  prior 
to  serumtherapy  the  death-rate  in  diphtheria  was  56  per  cent. 
and  bad  fallen  to  L6  per  cent,  after  the  introduction  of  this 
method. 

II,  is  at  present  generally  agreed  thai  u  'ruin  having  100  unit- 
is  a  very  efficacious  one,  viz.,  thai  I  c.cm.  is  sufficienl  to  aeutralize 
loo  toxic  units,  that  is,  looo  fatal  doses.  Such  is  the  strength  of 
the  serum  furnished  by  the  [nstitul  Pasteur.  'I'd''  Belgian  serum, 
prepared  under  the  direction  "I'  Punch  in  the  laboratory  of 
Leopold  Park,  has  a  power  of  '200.  In  Germany  the  laboratory 
of  Meister,  Lucius,  and  Urihiing,in  Hoechst,  furnishes  tin-'''-  varieties 
of  sera  in  vials  of  10  c.cm.  stamped  by  Hi'1  government.  Scrum 
No.  1  has  a  power  of  (io  units  per  c.cm.;  No.  2  is  equivalenl  to 
100  units,  and  No.  3  to  150.  The  ('(intents  of  one  vial,  Bay  10  c.cm., 
is  generally  injected,  and  one  of  these  three  varieties  is  employed 
according  to  certain  more  or  less  clearly  determined  condition-.  On 
the  one  hand,  the  dose  is  proportioned  to  the  age  and  weight  of  (In- 
patient; on  the  other  hand,  serum  No.  I  is  made  use  of  if  the  case 
is  of  moderate  gravity  and  treated  from  the  beginning.  If  the 
larynx  is  involved  and  if  three  or  four  days  have  already  elapsed, 
then  serum  No.  2  is  resorted  to.  No.  3  is  used  in  cases  of  extreme 
gravity.  In  France,  where  one  serum  only  is  employed,  the  dose 
is  diminished  or  increased  according  to  the  same  indications 
described  with  reference  to  the  German  method. 

In  order  to  appreciate  the  method  it  is  necessary  to  take  into 
account  a  number  of  factors  depending  upon  the  patient.  In  the 
first  place,  the  age  of  the  subject.  In  children  diphtheria  is  always 
more  serious  than  in  adults,  and  it  is  the  more  dangerous  the  younger 
the  child.  From  this  point  of  view  the  latest  German  statis 
are  altogether  convincing.  The  death-rate  is  still  as  high  as  41^ 
per  cent,  in  children  under  one  year  of  age.  From  one  to  two  years 
of  age  it  is  36.6  per  cent.  From  two  to  five  years  it  varies  from 
15  to  18  per  cent.  It  is  from  5  to  10  per  cent,  in  children  between 
five  and  fifteen  years  of  age.  It  then  falls  to  2.7  per  cent,  from 
fifteen  to  twenty  years  of  age.  and  to  0.8  per  cent,  from  twenty 
to  thirtjr  years  of  age.  The  best  results  are  observed  at  this  last- 
named  epoch  of  life.  Beyond  thirty  years  of  age  diphtheria  is  of  rarer 
occurrence,  but  it  is  graver.  The  death-rate  reaches  3.7  per  cent, 
between  thirty  and  forty  years  of  age,  and  to  9.1  per  cent,  after 
fifty  years  of  age. 

45 


706  INFECTIOUS  DISEASES. 

Although  the  mortality  remains  high  in  children,  it  is  among 
them  that  serumtherapy  renders  the  most  valuable  service.  In 
fact,  adults  recover  quite  often,  no  matter  what  the  treatment 
employed;  while  children  succumb  because  of  their  weak  resistance 
to  the  toxin  and  on  account  of  the  extension  of  the  process  into  the 
larynx.  Hence,  the  death-rate  is  relatively  less  affected  with  refer- 
ence to  adults.  It  is  reduced,  especially  in  children,  and  notably 
in  those  suffering  from  croup.  There  is,  however,  an  indispensable 
condition  for  success,  that  is,  intervention  as  earl)''  as  possible.  On 
this  point  all  clinical  observers  are  in  accord.  In  this  connection 
the  figures  of  the  German  statistics  are  highly  suggestive.  The 
death-rate  is  5.4  per  100  when  the  treatment  is  begun  on  the 
first  day,  and  6.7  per  cent,  when  it  is  instituted  on  the  second  day. 
It  rises  to  10  per  cent,  for  the  third  day  and  to  23  per  cent,  for 
the  fifth  day.  Prompt  intervention  has  the  double  advantage  of 
combating  the  disease  while  the  intoxication  is  as  yet  unpronounced 
and  secondary  infections  have  not  assumed  a  dangerous  character, 
and  by  neutralizing  the  toxin  early  certain  incidents  of  convales- 
cence, such  as  paralysis  are,  perhaps,  prevented. 

In  order  to  benefit  the  patient  as  promptly  as  possible  by  the 
effects  of  the  serum,  most  bacteriologists  advise  an  injection  as 
soon  as  there  is  the  slightest  doubt  as  to  the  nature  of  a  sore  throat, 
or  even  as  soon  as  any  exudate  whatever  is  present.  At  the  same 
time  a  culture  is  prepared  from  the  exudate,  and,  at  the  end  of 
twelve  to  fifteen  hours,  the  bacteriological  diagnosis  indicates  the 
nature  of  the  disease.  The  conduct  of  the  physician  is  thus  decidedly 
simplified.  These  principles,  however,  cannot  be  accepted  without 
some  reservation.  Here  we  touch  a  delicate  point  which  has  already 
given  rise  to  much  controversy.  For  my  part,  I  believe  that  physi- 
cians neglect  too  much  the  examination  of  the  patients  in  the 
belief  that  they  are  able  to  establish  a  diagnosis,  prognosis,  and 
therapeutic  indications  by  means  of  the  data  furnished  by  bacteri- 
ology. It  seems  to  me  that  the  diagnosis  of  diphtheria  is  not  as 
difficult  as  it  is  said  to  be.  In  our  isolation  wards,  where  we  receive 
all  cases  of  anginas  attended  by  the  slightest  whitish  exudate,  our 
pupils  are  accustomed  to  make  the  differential  diagnosis.  A  diag- 
nostic mistake  occurred  only  in  those  cases  of  benign  anginas  which 
were  cured  almost  without  any  treatment  after  cleansing  of  the  throat. 
Two  varieties  of  cases  are  observed  in  adults :  The  angina  may 
present  the  indisputable  characteristics  of  diphtheria.    The  serum 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  707 

is  then  i i ij ecte< I  forthwith,  and  :i  culture  prepared.  In  other  cs  e 
fche  wore  throat  has  the  aspect  of  an  herpetic  angina.  A  culture  mu  t 
be  made,  and  if  on  the  following  day  Loeffler's  bacillui  i  found, 
an  injection  may  be  made  if  necessary.  Such  ha  been  our  practise 
in  our  wards  reserved  Tor  adults.  In  the  case  of  children  more 
prompt  notion  is  required.  In  fact,  it  is  ;ii  thai  epoch  of  life  thai 
diphtheria  is  a  grave  disease.  The  com:-''  of  the  procet  musl  be 
arrested  from  the  beginning  and  involvement  of  the  larynx  pre- 
vented. From  this  standpoint  there  is  a  radical  difference  between 
diphtheria  of  children  and  that  <>1  adults.  In  adults,  diphtheria 
is  a  relatively  benign  malady  which  seldom  kills  of  itself  and  which 
is  particularly  dangerous  because  of  renal  complications  and  con- 
secutive paralysis.  Such  is  not  the  case  with  children.  II 
soon  as  there  is  the  slightest  doubt,  serum  injections  must  be  re- 
sorted to.  The  few  inconveniences  of  the  serumtherapy  method, 
the  accidents  which  it  may  produce,  and  which  will  be  referred  to 
in  the  following  chapter,  are  nothing  in  the  presence  of  the  urgency 
for  prompt  action.  To  wait  for  the  result  of  the  cultures  would  be 
to  lose  valuable  time,  the  more  valuable  as  it  occasionally  happens 
that  no  colony  develops  at  the  end  of  twelve  or  even  twenty-four 
hours.  In  brief,  in  the  case  of  a  child  presenting  the  clinical  signs 
of  diphtheritic  angina,  and  especially  of  croup,  serumtherapy 
must  be  applied  immediately.  In  cases  of  pseudomembranous 
angina  presenting  the  characters  of  herpetic  sore  throat  clinically 
not  resembling  diphtheria,  it  is  usually  permissible  to  wait  for  the 
result  of  cultivation,  and,  when  one  has  a  certain  amount  of  experi- 
ence in  diphtheria,  bacteriological  examination  will  confirm  the  data 
of  observation.  In  order  to  comprehend  the  action  of  the  serum 
we  must  study  successively  the  modifications  which  occur  in  the 
local  and  general  state  of  the  patient.  Locally,  the  serum  cai  -  - 
exfoliation  of  the  pseudomembrane.  Very  often  the  aspect  is 
completely  changed  at  the  end  of  twenty-four  hours.  The  exudates 
are  softened,  deliquescent,  and  the  throat  begins  to  be  relieved  of 
congestion.  It  is  well  to  remember,  however,  that  on  the  day 
following  the  injection  an  increase  in  the  extent  of  the  pseudo- 
membrane  may  occur,  for  the  reason  that  the  parts  were  already 
invaded  by  the  bacillus,  and  the  exudate  was  produced  in  spite  of 
the  action  of  the  serum.  Coincident \y,  the  engorgement  of  the 
lymphatic  glands  diminishes.  Four  or  five  days  are  generally  required 
for  the  complete  disappearance  of  the  exudates.     They  sometimes 


708  INFECTIO  US  DISEASES. 

persist  for  a  longer  period,  for  a  week  or  more;  but  they  are  then 
less  extensive,  occupying  only  a  part  of  the  tonsils,  and  the  state 
of  the  patient  causes  no  anxiety.  While  the  local  lesions  subside, 
the  general  state  improves.  The  patients  experience  a  feeling  of 
exhilaration,  and  the}7  feel  that  the  disease  is  checked.  In  conse- 
quence of  the  injection  a  profuse  perspiration  often  occurs,  which  is 
a  happy  phenomenon,  since  it  seems  that  sweating  eliminates  the 
toxin.  The  influence  upon  the  temperature  is  variable.  The  serum 
frequently  produces  a  transitory  febrile  movement,  and  if  fever 
existed  it  falls  at  the  end  of  twenty-four  hours,  while  at  the  same 
time  the  frequency  of  the  pulse  diminishes. 

If  the  case  is  one  of  laryngeal  diphtheria  the  result  is  more  re- 
markable b}T  curtailing  the  duration  of  the  evolution  and  favoring 
elimination  of  the  pseudomembranes.  Serumtherapy  has  left  no 
longer  any  occasion  for  tracheotomy.  The  method  of  intubation 
has  been  resumed.  This  change  in  operative  procedures  has  several 
advantages.  Tracheotomy  is  not  only  dangerous,  but  by  opening 
the  trachea  it  permits  the  penetration  of  external  germs  or  of 
microbes  present  in  the  wound,  and  thus  favors  the  development 
of  bronchopneumonia.  Besides  these  immediate  accidents,  it  may 
give  rise  to  some  remote  ones.  According  to  Landouzy,  a  great 
number  of  tracheotomized  patients  die  at  a  later  period  in  conse- 
quence of  the  development  of  pulmonary  tuberculosis. 

While  there  is  universal  agreement  as  to  the  facts  above  reported, 
doubt  arises  when  we  consider  the  role  of  the  serum  with  respect 
to  certain  complications  or  grave  manifestations,  such  as  albumin- 
uria. This  question  requires  new  investigation.  At  present  it  is 
impossible  to  form  an  opinion  in  view  of  all  sorts  of  contradictory 
assertions.  Some  authorities  contend  that  the  serum  prevents  or 
diminishes  diphtheritic  albuminuria.  Others,  taking  ground  upon 
some  experiments,  assert  that  the  serum  gives  rise  to  renal  alter- 
ations. All  that  is  possible  to  state  is  that  albuminuria  does  not 
constitute  a  contraindication  to  serumtherapy.  On  the  contrary, 
diphtheritic  albuminuria,  indicating  a  profound  intoxication  of  the 
organism,  demands  active  intervention.  The  serum  cannot,  of  course, 
overcome  pre-existing  renal  lesions.  The  important  fact  to  observe 
is  that  serumtherapy  does  not  aggravate  it.  Clinical  facts  are  far  too 
complex  to  permit  a  decisive  opinion.  The  question  should  be  taken 
up  experimentally  to  determine  whether  antidiphtheritic  serum  gives 
rise  to  renal  lesions  or  aggravates  pre-existing  alterations  in  animals . 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  709 

As  to  paralyses,  I  hey  are  s1  ill  quite  frequenl .    hi   hoped,  I 
thai-  when  serumtherapy  is  promptly  applied  while  the  toxins  are 
not  yet  abundant  and  the  nervou  i  elements  are  more  re  i  tant,  the 
accidents  will  diminish. 

Wo  have  thus  far  endeavored  to  sum  up  the  advants 
diphtheritic  serum,  disregarding  the  accidents  which  may  be  attrib 
utod  to  its  use  and  which  will  be  Btudied  later  on.    We  have  ihown 
what  should  bo  the  lino  of  oondud  a    regards  the  opportune 
Injection.    The  question  of  concomitanl  treatmenl  now  remaini  to 
be  considered. 

It  has  been  asserted  that  antiseptic  lavage  of  tho  Ihroal  hin 
the  action  of  the  serum,  and  many  physicians  al  presenl  op 
forcible  removal  of  pseudomembranes.  If  seems  to  me  thai  one 
should  not  have  any  preconceived  ideas  on  these  questions,  h  is 
better  to  be  guided  by  observation  of  each  patient.  All  that  can 
be  said  is  thai  in  the  treatmenl  of  diphtheritic  anginas  of  adults 
we  have  obtained  excellent  results  by  means  of  lavage  with  boiled 
water,  with  solutions  of  carbolic  acid  and  thymol,  or  cleansing  with 
lemon  juice.  Finally,  in  certain  cases  we  have  noticed  that  con- 
comitant injections  of  pilocarpine  manifestly  favor  the  action  of 
the  serum.  The  injections,  which  have  been  so  fiercely  opposed, 
seem  to  produce  favorable  results,  provided  the  state  of  the  heart 
and  of  the  kidneys  be  carefully  watched.  When  the  heart  is  strong 
and  the  urine  is  not  albuminous,  the  injection  of  one  centigram  of 
nitrate  of  pilocarpine  rapidly  ameliorates  the  general  state  and 
favors  detachment  of  the  pseudomembranes.  In  the  case  of  adults 
it  is  a  good  auxiliary  to  serumtherapy,  at  least  in  certain  instanc 

Leprosy,  Glanders.  A  few  serumtherapy  attempts  were  made  by 
Garrasquilla  against  leprosy.  The  serum  caused  the  return  of  sensi- 
bility, and  the  disappearance  of  the  spots,  edema  and  tubercles,  and 
cicatrization  of  ulcerations,  etc. 

Few  researches  have  been  pursued  on  the  serumtherapy  of  glan- 
ders. We  have  no  others  to  cite  except  those  of  Chenot  and  Picq, 
who,  out  of  ten  inoculated  animals,  cured  seven  by  injecting  into 
them  the  serum  of  cattle,  that  is,  a  species  naturally  refractory  to 
the  disease. 

Bubonic  Plague.  Yersin,  Calmette,  and  Borrea  succeeded  in 
immunizing  animals  against  bubonic  plague  by  means  of  repeated 
inoculations  of  cultures  heated  for  an  hour  at  a  temperature  of 
136.4°  F.  (5S°  C).     Dr.  Roux  has  likewise  immunized  horses  with 


710  IXFECTIO  US  DISEASES. 

toxins.  The  serum  thus  obtained  gave  good  results  in  inoculated 
monkeys  (Wyssokowitz).  In  man  it  confers  an  immunity  which 
lasts  for  about  a  fortnight.  The  therapeutic  attempts  made  by 
Yersin  in  India  reduced  the  death-rate  from  80  to  49  per  cent. 
In  China,  out  of  twenty-six  sufferers  treated  in  1897,  only  two 
deaths  occurred. 

Pneumococcosis.  The  study  of  antipneumococcic  serumtherapy 
has  given  rise  to  a  great  number  of  researches,  of  which  Dr.  Mosny 
speaks  in  a  review.1  As  this  author  remarks,  animals  may  be 
immunized  by  several  procedures :  One,  accidentally  discovered  by 
A.  Fraenkel,  and  systematically  employed  by  some  experimenters, 
consists  in  injecting  dilutions  of  virulent  microbes.  It  seems  that, 
in  order  to  succeed,  it  is  necessary  to  employ  cultures  of  moderate 
strength,  for,  according  to  Foa  and  Scabia,  the  highly  virulent 
agents  kill  the  animals  or  produce  no  effect  at  all — i.  e.,  do  not 
immunize  them.  The  attenuated  cultures  gave  satisfactory  results 
in  the  hands  of  Netter,  Emmerich,  Fowitzky,  Foa,  and  Scabia. 

Cultures  sterilized  by  filtration  or  by  the  addition  of  a  little 
chloroform  are  generally  employed,  but  they  must  be  heated  to 
140°  to  149°  F.  (60°  to  65°  C).  Without  this  precaution  the  fluid 
is  highly  toxic  and  seldom  immunizing.  As  in  the  case  of  diphtheria, 
the  toxin  may  also  be  modified  by  means  of  the  iodo-iodide  reagent ; 
an  immunity  persisting  for  three  months  is  thus  obtained  (Foa  and 
Carbone).  Finally,  for  securing  good  results  it  is  necessary  to 
immunize  by  means  of  microbes  possessing  about  the  same  virulence 
as  those  against  which  the  animals  are  to  be  protected.  It  is  like- 
wise possible  to  immunize  animals  by  means  of  filtered  macerations 
of  the  organs  of  rabbits  dead  from  pneumococcic  septicemia  (Mosny), 
by  means  of  sterilized  sputa  or  exudates,  the  blood  serum  or  the 
serum  produced  by  vesicatories  (Klemperer).  Whatever  the  mode 
of  vaccination,  the  serum  of  animals  that  have  been  rendered 
refractory  becomes  immunizing  and  conservative. 

Pneumococcic  diseases  being  often  benign  in  man,  a  serum  of  mod- 
erate activity  may  render  great  therapeutic  services.  It  hastens 
recovery  toward  which  the  natural  forces  of  the  organism  tend. 

G.  and  F.  Klemperer  undertook  the  first  practical  applications. 
After  injecting  themselves  with  from  0.5  c.cg.  to  3  c.cg.  of  serum  of 
immunized  rabbits,  and  thus  proving  the  innocuity  of  the  fluid,  they 

1  Mosny.  La  vaccination  et  la  gu6rison  de  Pinfection  pneumococcique  exp6rimentale 
et  de  la  pneumonie  franche  de  l'konxme.     Arch,  de  m£d.  exp6r.,  1893,  p.  259. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  711 

injected  from  r>  c.cm.  to  LO  c.cm.  into  patient  offering  from  typhoid 
fever.  The  result  was  negative.  They  then  operated  upon  six  pneu- 
monia patients,  and  with  from  I  c.cm.  to  6  c.cm.  of  serum  obtained 
a  fall  in  the  temperature,  [n  two  cases  the  di  ea  ewa  immediately 
arrested,  [n  another  scries  of  twelve  ca  e  G.  Klemperer  liki 
observed  very  pronounced  amelioration  with  doses  varying  from 
5  c.cm.  to  LO  c.cm.  Facts  subsequently  published  by  Foa  and  Car- 
bone,  Foa  and  Scabia,  and  Janson  are  no  less  encouraging.  By  tabu- 
lating the  observations  of  these  various  authors  the  writer  fincle  a 
total  of  thirty-nine  cases.  In  only  one  case  (an  observation  of  Janson 
the  result  was  nil.  In  all  the  other  cases  there  was  very  marked 
improvement.  In  twenty-one  cases  the  crisis  was  produced  on  the 
following  day  or  two  days  after  intervention/  and  in  several  casee  on 
the  sixth,  fifth,  and  even  the  fourth  day.  In  view  of  such  data  it 
is  difficult  not  to  admit  the  favorable  action  of  the  serum. 

Not  only  the  serum  of  rabbits  but  also  that  of  man  may  serve  for 
therapeutic  purposes.  In  some  unpublished  experiments,  the  results 
of  which  were  indicated  in  a  memoire  of  Prof.  Bouchard,  we  recog- 
nized with  Dr.  Charrin  that  "the  injection  into  rabbits  of  blood 
serum  obtained  by  venesection  from  a  man  suffering  from  pneumonia 
in  the  stage  of  defervescence  or  seven  days  after,  renders  these  ani- 
mals refractory  to  inoculation  with  pneumococcus,  and  this  four  days 
and  even  eleven  days  after  the  injection  of  the  serum."1  Andeoud2 
applied  these  experimental  results  to  man.  He  injected  into  two 
patients  the  serum  drawn  from  a  pneumonia  convalescent.  In  one 
of  the  cases  two  injections  sufficed  to  bring  about  a  crisis  on  the 
sixth  day.  In  the  other  instance  the  disease  terminated  on  the  fifth 
day,  fifteen  hours  after  the  first  injection.  In  a  communication 
addressed  to  the  Congress  of  Rome,  Maragliano  announced  that  he 
had  obtained  thirty-nine  favorable  results  by  the  employment  of  the 
serum  of  immunized  animals  or  of  cured  patients.  In  attempts  of 
this  kind,  however,  the  serum  of  the  dog  should  never  be  resorted 
to.  This  serum,  far  from  preventing  the  infection  of  the  rabbit, 
favors  it.  An  observation  of  Foa  and  Scabia  proves  that  it  acts  in 
the  same  manner  upon  man.  An  injection  of  2  c.cm.  or  3  c.cm.  of 
the  serum  of  a  dog  which  had  previously  received  virulent  cultures 

1  Bouchard.      Sur  les   pretendues   vaccinations   par  le   sang.      Revue  de   m^decine, 
January,  1892,  p.  15. 

2  Andeoud.  Serotherapie  dans  la  pneumonic.  Revue  med.  de  la  Suisse  romande, 
February.  1893. 


7 1 2  INFECTIO  US  DISEASES. 

of  pneumococci,  caused  a  notable  aggravation  of  the  general  phe- 
nomena, an  increase  in  the  fever,  and  a  manifest  delay  in  recovery. 

Although  pneumonia  is  a  disease  which,  in  the  majority  of  cases, 
naturally  terminates  in  recovery,  there  are  other  pneumococcic  mani- 
festations which  almost  invariably  cause  death.  Meningitis  is  among 
the  number.  Here  is  a  subject  for  investigation  which  is  of  great 
importance  and  necessarj7  for  a  final  judgment  of  the  value  of  serums. 
In  fact,  there  is  already  a  recorded  observation  which,  although 
unique,  is  none  the  less  encouraging.  Righi1  observed  a  seven-year- 
old  child  presenting  the  typical  symptoms  of  acute  meningitis. 
Examination  of  the  blood  revealed  the  presence  of  the  pneumococcus. 
On  the  fifth  day  the  author  injected  1  c.cm.  of  serum  taken  from  a 
convalescent  of  pneumococcic  meningitis.  The  symptoms  improved 
and  the  patient  recovered  on  the  eighth  day.  The  serum  injected 
was  endowed  with  energetic  germicidal  properties  and  proved  to  be 
preservative  and  curative  for  mice  and  rabbits. 

Proteobacillosis.  It  has  long  been  known  that  it  is  possible  to 
immunize  against  the  proteus  with  soluble  substances  or  even  well- 
defined  products  like  neuridin.  De  Nittis2  has  made  known  a  mode 
of  immunization  by  means  of  living  cultures  and  succeeded  in  obtain- 
ing an  active  serum.  He  showed  that  the  guinea-pig  could  endure 
an  intraperitoneal  injection  of  from  3  c.cm.  to  3.5  c.cm.  of  a  culture 
1.5  c.cm.  to  2  c.cm.  of  which,  when  introduced  by  the  veins,  killed 
rabbits  weighing  2  kilograms  within  twenty-four  hours.  The  serum 
of  guinea-pigs  thus  treated  proved  to  be  very  efficacious.  A  dose  of 
2  c.cm.  per  kilogram  of  animal  suffices  to  protect  rabbits  against 
inoculations  which  kill  the  controls  in  twenty-four  hours. 

Pyocyanobacillosis.  Pyocyanobacillosis  or  pyocyanic  disease  has 
been  the  subject  of  important  serumtherapic  investigations.  The 
experiments  pursued  by  Bouchard3  led  this  scientist  to  formulate 
certain  conclusions,  several  of  which  were  then  absolutely  new,  and 
which,  from  the  standpoint  of  general  pathology,  are  of  such 
importance  that  it  will  be  interesting  to  give  a  resume  of  them  here. 

After  determining  that  the  blood  of  naturally  immune  animals  has 
but  a  slight  therapeutic  action,  and  that,  in  order  to  obtain  an  effi- 
cient serum,  it  is  necessary  to  employ  the  blood  of  immunized  animals, 

1  Pdghi.    La  sieroterapia  nella  meningite.    La  riforma  medica,  1894,  iii.  p.  566. 

2  De  Nittis.     Serotherapie  du  Proteus  vulgaris.     Societe  de  biologie,  June  13,  1896. 

3  Bouchard.  Les  pretendues  vaccinations  par  le  sang.  Revue  de  medecine,  January, 
1892. 


THERAPEUTICS  OF  INFECTIOUS  DISEA8E8.  71.', 

Bouchard  demonstrated  that  the  serum  i  a   actives  ,  and  even  more 
energetic  than,  defibrinated  blood,    tn  order  to  prove  thai  the  ei 
were  due  to  the  serum,  viz.,  to  soluble  matter   andnol  to  morpho- 
logical elements,  this  author  filtered  the  fluids  through  porcelain. 
The  results  were  not  modified.    I  [e  then    I  udied  the  urine  of  animals 
which  had  received  blood  of  immunized  animals  and  found  thai  it 
did  not  confer  immunity.    It  did  nol  acl  otherwise  than  the  urine 
of  animals  into  which  sterilized  cultures  had  been  injected.    More- 
over, he  showed  that  the  immunity  conferred  by  the  -••nun 
short  duration.    If  it  existed  on  the  eighteenth  day  il  disappeared 
on  the  twenty-second.    The  serum  exerts  an  immediate  protective 
action  which  gradually  diminishes,  while  the  bacterial  substanc 
first  weaken  the  resistance  and  subsequently  increase  it.    Hence  it 
may  be  concluded  thai  the  active  substance  of  the  serum  is  rapidly 
destroyed  within  the  organism  of  the  animal  into  which  the  injection 
has  been  made,  and  that  the  immunity  produced  by  the  serum  is  due 
not  to  a  reaction  of  the  organism,  but  simply  to  the  introduction  of 
some  germicidal  substance.    Finally,  a  last  distinction  must  be  es1  ab- 
lished  between  the  immunizing  substances  of  cultures  and  th< 
the  serum.    The  former  resists  a  temperature  of  239°  F.  (115 *  I 
the  latter  are  destroyed  between  140°  F.  and  149°  F.  (60°  C.  and 
65°  C),  and  at  the  same  time  the  germicidal  action  disappear.-. 

Staphylococcosis.  The  first  experimental  attempt  of  serumtherapy 
was  directed  against  the  staphylococcus.  Hericourt  and  Richet,  in 
a  study  on  the  staphylococcus  pyosepticus,  which  is  a  variety  of  the 
staphylococcus  alhus,  recognized  that  infection  in  a  rabbit  could  be 
prevented  by  injecting  the  blood  of  dogs.  The  result  was  especially 
manifest  when  use  was  made  of  dogs  that  had  recovered  from  a 
previous  inoculation  of  staphylococci. 

The  method,  which  consists  in  employing  the  serum  of  animals 
cured  from  a  virulent  inoculation,  is  too  uncertain  for  generalization. 
It  was,  therefore,  necessary  to  immunize  by  the  usual  procedures, 
notably  with  sterilized  cultures.  Drs.  Rodet  and  Courmont  discov- 
ered the  interesting  fact  that  the  soluble  products  of  staphylococci. 
far  from  increasing  the  resistance,  diminished  it  and  predisposed  the 
organism  to  infection.  By  continuing  their  researches,  however,  they 
succeeded,  by  means  of  alcohol,  in  extracting  a  substance  capable  of 
conferring  upon  animals  a  sufficiently  marked  immunity.  Dr.  Cour- 
mont subsequently  learned  that  the  serum  of  animals  thus  prepared 
has  no  germicidal  power,  but  possesses  the  property  of  attenuating 


714  INFECTIOUS  DISEASES. 

microbes  and  causing  them  to  lose  their  virulence.  The  practical 
importance  of  this  result  is  evident. 

It  is  not  only  by  employing  substances  soluble  in  alcohol  that 
animals  may  be  immunized.  Yiquerat  arrived  at  the  same  result  by 
a  procedure  first  employed  by  Behring.  Viquerat  injected  a  1 :  2000 
solution  of  trichloride  of  iodine  into  the  neighborhood  or  the 
interior  of  a  staphylococcic  abscess.  Under  the  influence  of  this 
treatment  the  abscess  was  rapidly  cured,  and  its  contents  were  trans- 
formed into  a  serum  which  was  filtered  in  order  to  free  it  from 
microbes  which  it  might  contain.  This  fluid,  like  the  blood  serum 
of  cured  individuals,  possesses  preventive  properties  against  the 
intravenous  inoculation  of  staphylococci  in  rabbits.  Having  thus 
obtained  a  serum  of  a  preventive  power  of  ttfoU;  the  author  in- 
jected from  10  c.cm.  to  65  c.cm.  of  it  into  various  patients,  and 
obtained  a  speedy  cure  of  furuncles,  paronychia,  and  even  osteomye- 
litis. He  next  immunized  animals  by  means  of  cultures  to  which 
trichloride  of  iodine  was  added,  and  obtained  from  goats  a  serum 
endowed  with  a  power  of  from  10,000  to  500,000.  When  injected 
into  patients  this  serum  caused  a  very  intense  reaction  at  the  point 
of  the  lesion.  At  the  end  of  fifteen  or  twenty  hours  the  phenomena 
improved  and  notable  amelioration  resulted.  Finally,  Kose  immun- 
ized a  goat  by  first  injecting  it  with  cultures  attenuated  by  heat,  then 
more  and  more  virulent  fluids.  The  serum  of  this  animal,  although 
devoid  of  all  germicidal  action,  increased  the  resistance  of  inoculated 
rabbits,  but  did  not  save  them ;  they  died  less  rapidly,  however,  than 
the  controls.    It  is  true  that  the  goat  was  insufficiently  immunized. 

Streptococcosis.  The  history  of  antistreptococcic  serumtherapy  has 
been  presented  in  such  a  faulty  way,  except  in  Bonnet's1  work,  that 
we  think  it  worth  while  to  re-establish  the  succession  of  investiga- 
tions by  indicating  the  dates. 

In  order  to  prepare  an  efficient  serum  it  is  always  necessary  to 
reinforce  the  immunity  of  the  animals.  Several  procedures  were  used 
with  quite  variable  results.  We  may  group  the  attempts  in  the 
following  manner : 

1.  Immunization  by  Living  Cultures.  Lingelsheim,2  who  employed 
all  cultures  heated  to  145.4°  F.  (63°  C.)  for  an  hour,  obtained  only 

1  Bonnet.  La  serumtherapie  dans  les  affections  streptococciques.  Gazette  hebdoma- 
daire,  1895,  p.  229. 

2  Lingelsheim.  Exp.  Untersuchungen  uber  morpholog,  cultur,  und  patholog.  Eigen- 
schaften  verschiedener  Streptokokken.     Zeitschr.  f.  Hygiene,  Bd.  x.,  Heft  2,  1891. 


THEEAPEUTIOS  OF  INFECTIOUS  DISEASES.  71fi 

negative  results.  Willi  cultures  attenuated  according  to  Behring't 
procedure,  viz.,  by  means  <>r  trichloride  of  iodine,  he  succeeded  in 
immunizing  only  two  mice  out  of  twelve.  By  operating  upon  rabbits, 
De  P.'iolis1  rendered  the  animals  refractory  by  injecting  into  their 
veins  non-virulent  cultures.     We  succeeded  in  conferring  immunity 

upon  .'uiini.'i.ls  by  making  successive  inoculations  of  virulent  cultures 

beneath  the  skin  of  their  ears.  The  reactions  were  le  and  less 
intense  and  finally  became  so  mild  ;is  to  give  rise  only  to  circum- 
scribed abscesses.2 

2.  Immunization  by  Sterilized  Cultures.  As  in  other  infectii 
immunity  from  streptococcic  infection  may  be  conferred  by  means 
of  soluble  products.  A  little  difficulty  is  encountered  here.  Sterilized 
cultures  contain  two  groups  of  substances  with  antagonistic  action. 
Some  of  them  diminish  resistance.  Others  increase  it.  If  from 
5  c.cm.  to  12  c.cm.  of  :i  culture  filtered  through  porcelain  be  injected 
into  animals,  subsequent  inoculation  of  the  living  microbe  produces 
death  far  more  rapidly  than  when  no  previous  intervention  had 
taken  place 

In  one  case  we  saw  an  animal  thus  succumb  eleven  times  more 
rapidly  than  the  control.  It  is  to  be  noted  that  no  relationship 
exists  between  the  quantity  of  the  toxic  substance  injected  and  the 
degree  of  predisposition  created  by  its  injection.  If, however,  cultures 
sterilized  by  heat  are  employed,  the  effects  are  quite  different.  Rab- 
bits which  received  from  5  c.cm.  to  30  c.cm.  of  the  fluid  thus  obtained, 
and  which  were  inoculated  from  four  to  thirty  days  later,  survived 
while  the  controls  died  within  a  few  days.3 

We  must  remark,  however,  that  these  results  are  perhaps  appli- 
cable only  to  rabbits  or  at  least  to  certain  animal  species.  There  are 
others  in  which  injections  of  filtered  cultures  seem  to  increase  the 
resistance.  Such  is  the  case  with  the  horse.  On  the  other  hand,  the 
emplojanent  of  cultures  sterilized  by  heat  is  not  without  danger. 
Very  virulent  cultures,  or  even  cultures  of  moderate  activity  in  which 
certain  varieties  of  streptococci  are  developed,  contain  noxious  sub- 
stances which  cannot  be  destroyed  by  heat.  Under  these  conditions 
their  injection  gives  rise  to  emaciation,  at  times  cachexia  and  death, 

1  De  Paolis.    Sulla  proprieta  vaceinale  dello  streptococco  dell'  erisipela.     La  riforma 
niedica,  1SS9,  No.  200. 

2  Roger.     Modifications   du   serum   &  la   suite   de   l'erysipele.     Society   de   biologie, 
October  25,  1S90. 

8  Roger.     Action  des  produits  solubles  du  streptocoque  de  l'erysipele.     Society  de 
biologie,  July  4,  1S91. 


716  INFECTIO  US  DISEASES. 

and  may  fail  to  confer  immunity.  These  remarks  account  for  a 
great  many  contradictory  facts. 

3.  Immunization  by  Mixed  Procedures.  Mironoff1  obtained  good 
results  by  combining  the  proceedings  hitherto  described.  He  em- 
ployed successively,  in  the  same  animal,  attenuated  cultures  and 
virulent  cultures  in  progressively  increasing  doses.  He  thus  suc- 
ceeded in  rendering  animals  able  to  bear,  without  reaction,  quan- 
tities of  virulent  cultures  ten  times  larger  than  those  which  are  fatal 
for  the  non-immunized. 

Whatever  the  method  employed  for  immunizing  animals,  the 
serum  of  the  vaccinated  acquires  therapeutic  properties.  This  was 
proved  by  the  author's  experiments2  and  by  those  of  Mironoff.3  Ac- 
cording to  this  author  the  action  of  the  serum  is  proportionate  to  the 
dose  employed;  but  it  does  not  affect  the  local  lesions.  As  the  result 
of  extremely  remarkable  researches,  Marmorek4  succeeded  in  pre- 
paring a  serum  by  means  of  cultures  of  incredible  virulence.  To  kill 
a  rabbit  a  dose  of  0.000,000,000,01  c.cm.  of  the  culture  is  sufficient. 
The  rabbits  into  which  the  serum  is  injected  a  few  hours  before  the 
inoculation  resist  this  microbe.  Those  that  are  first  inoculated  and 
then  treated  a  few  hours  later  also  survive.  Finally,  Parascandolo 
immunized  animals  against  the  staphylococcus  and  streptococcus. 
He  employed  highly  virulent  microbes  which  he  cultivated  in  bouil- 
lon containing  sugar.  The  cultures  sterilized  by  the  addition  of  5  per 
cent,  of  phenol  were  injected  into  dogs,  rabbits,  and  guinea-pigs  in 
progressively  increasing  doses.  The  serum  of  animals  thus  prepared 
neutralizes  in  vitro  the  toxins  and  the  microbes;  its  action  proved 
preventive  and  curative  in  animals  into  which  these  pyogenic  mi- 
crobes were  inoculated  and  had  caused  either  a  generalized  infec- 
tious process,  such  as  puerperal  fever  or  septicemias,  or  a  localized 
process  like  erysipelas. 

What  renders  these  investigations  interesting  is  the  fact  that  this 
author  succeeded  in  cultivating  several  pyogenic  microbes  in  the 
same  medium,  and  thus  obtained  a  serum  which  was  efficacious 
against  species  that  are  often  found  associated. 

1  Mironoff.  Immunisation  des  lapins  contre  le  streptocoque.  Arch,  de  medecine 
exper.,  1893,  p.  441. 

2  Roger.  Contribution  a  Petude  experimentale  du  streptocoque  de  Perysipele.  Revue 
de  medecine,  1892,  p.  953. 

8  Mironoff.     Loc.  cit.,  1893. 

*  Marmorek.  Sur  le  streptocoque.  Societe  de  biologie,  February  23,  1895.  Strep- 
tocoque et  serum  antistreptococcique.    Annales  de  l'Institut  Pasteur,  July,  1895,  p.  593. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  717 

Thus  a  number  of  experimenters  arrived  independently  at  identical 

conclusions,  viz.,  possibility  of  vaccinating  animal  against  the 
streptococcus;  possibility  of  preparing  a  scrum  efficacious  against 
experimental  streptococcic  infections. 

Hence,  it  w;ls  natural  to  attempt  Hie  treatment  by  antistri 
coccic  serum  in  human  diseases.    The  first  endeavor  wb    ma 
Gramakowsky,  who  treated  two  cases  of  erysipelas.    The  result 
not  very  encouraging,  since  (me  of  the  patient    died.    On  February 

23,  1X95,  wo  reported  to  llie  Kiological  Society  two  successes  ob- 
tained in  the  wards  of  I )r.  ( 'liniiin.1  They  were  two  women  suffering 
from  puerperal  fever,  one  of  them  profoundly  infected,  Both 
survived.  The  following  month  we  reported  two  other  cases,  and 
on  the  same  day  Dr.  Marmorek2  announced  that  he  hud  successfully 
treated  forty-six  patients  suffering  from  erysipelas.  From  this 
moment  on  contributions  succeeded  each  other  in  Franco  as  well 
as  in  other  countries.  The  results  were  quite  variable  and  i 
rise  to  a  good  deal  of  discussion. 

In  order  to  practise  serumtherapy  on  man  it  has  been  necessary 
to  resort  to  animals  capable  of  furnishing  great  amounts  of  blood. 
Hence,  the  horse  was  chosen. 

Following  the  suggestions  drawn  from  our  investigations  upon 
rodents,  we  immunized  animals  by  means  of  streptococcic  cultures 
sterilized  by  heat.  It  is  likewise  possible  to  confer  immunity  by 
means  of  toxins  obtained  by  nitration  of  the  cultures  through 
porcelain.  Dr.  Vinay  resorted  to  the  latter  procedure.  Finally, 
Marmorek  injected  into  the  veins  progressively  increasing  doses  of 
living  cultures  of  his  highly  virulent  streptococcus. 

All  these  methods  are  evidently  good.  Drs.  Denys,  Leclef,  and 
Marchand,  who  took  up  the  question  and  prepared  serums  by  means 
of  living  cultures  or  of  toxins,  obtained  very  encouraging  results 
in  both  cases.  The  only  point  that  now  requires  investigation  is 
whether  the  serums  are  more  efficacious  when  they  are  prepared 
by  one  or  the  other  of  these  various  procedures  and  whether  all 
are  equally  harmless.  The  serum  obtained  by  means  of  living 
cultures  has  at  times  caused  abscesses  and  erysipelas  patches  at 
the  point  of  injection.  This  result  is  due  to  the  persistence  of  the 
streptococci.     This  inconvenience  is  not.  however,  of  a  nature  to 

1  Charriu  et  Roger.  Essai  d 'application  de  la  serumtherapie  an  traitement  de  la  fidvre 
puerperale.     Soeiete  de  biologie,  February  23,  1S95.  p.  124. 

3  Marmorek.     Le  s£rum  antistreptococcique.     Ibid..  March  SO.  1S95.  p.  230. 


718  INFECTIOUS  DISEASES. 

cause  abandonment  of  the  method,  but  it  is  well  to  be  aware  of  the 
fact  and  take  some  precautions — to  wait  longer  before  bleeding  the 
animals  or  to  filter  the  serum  through  porcelain. 

In  order  to  prove  the  action  of  the  serum  it  was  thought  that 
cases  of  erysipelas  should  be  experimented  upon.  Hence,  Dr. 
Chantemesse  employed  the  serum  of  Marmorek  in  501  cases,  and  the 
death-rate  was  2.59  per  cent.  A  close  examination  of  these  facts 
permits  a  division  of  them  into  three  groups:  The  first  includes 
those  cases  in  which  the  serum  employed  had  a  strength  of  1  per 
7000,  with  a  death-rate  of  1.68  per  cent.  The  second  comprises 
those  cases  in  which  the  serum  had  a  strength  of  1  per  2000,  with  a 
mortality  reaching  6.54  per  cent.,  that  is,  a  far  greater  percentage 
than  by  usual  treatment.  Finally,  by  a  new  serum  having  a  strength 
of  1:30,000  the  death-rate  fell  to  1.03  per  cent. 

Some  objections  were  raised  against  these  results.  Dr.  Bolognesi 
remarked  that  just  as  favorable  results  may  be  obtained  by  the 
simplest  treatment.  In  the  wards  of  Juhel-Renoy  the  death-rate 
did  not  exceed  3.5  per  cent.,  and  occasionally,  it  fell  to  1.21  and 
even  to  0.9  per  cent.  As  a  matter  of  fact,  it  is  evident  that  an 
adult  of  good  constitution  does  not  generally  die  from  erysipelas. 
The  aged  persons  who  succumb  had,  for  the  most  part,  some  organic 
lesion,  particularly  of  the  liver. 

The  serum  should,  therefore,  be  reserved  for  grave  cases  in  which 
it  may  render  service,  for  cases  characterized  by  relapses  and  in 
prolonged  forms,  as  well  as  for  erysipelas  of  the  newborn,  although 
in  this  last  instance  it  does  not  seem  to  be  very  efficient. 

The  action  of  the  serum  in  cases  of  surgical  and  puerperal  septi- 
cemias deserves  particular  study.  Puerperal  fever  is  of  far  more 
frequent  occurrence  than  is  generally  believed.  From  1884  to  1893 
the  statistics  of  the  city  of  Paris  registered  3000  deaths  due  to  this 
cause.  This  is  under  the  real  figures,  as  a  good  many  cases  go  under 
different  designations.  The  results  obtained  with  the  serumtherapy 
treatment  have  been  quite  variable.  This  could  be  well  foreseen, 
since  intervention  takes  place  too  tardily  in  most  cases,  or  the  case 
is  one  of  mixed  infection,  or  perhaps,  insufficient  doses  of  the  serum 
are  employed.  After  the  publication  of  our  results  very  encouraging 
observations  were  reported  by  Drs.  Josue  and  Herniary,  Jacquot, 
Marmorek,  Chrobak,  Vinoy,  Denys,  and  Leclef  .*    On  the  other  hand, 

1  Denys  and  Leclef.  Sur  le  serum  antistreptococcique  (report  by  Rommelaere) . 
Acad,  de  Med.  de  Belgique,  December  28,  1895. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  719 

in  tin;  Obstetrical  Society  of  France  (April,  L896),  the  majority 
obstetricians  related  rather  disappointing  observation  .  Charpentier 
had  had  a  death  rate  of  35  per  cent.,  Bar  and  Ti  Bier  60  peT  cent. 
In  the  cases  which  we  treated  the  re  all  were  far  better.  Our 
statistics,  which  have  the  defecl  of  being  too  small,  containing  only 
twelve  cases  of  puerperal  fever,  may  be  divided  into  »ups: 

Those  in  which  ihi'  treatment  was  insufficienl     i.  e.}  in  which  too 
small  amounts  of  serum  were  injected.    Such  were  twi  one 

of  whom  died.  In  the  other  ten  cases  the  treatment,  which  was 
at  times  tardily  instituted,  yielded  nine  recoveries  and  only  one 
death.  Several  of  these  patients  would  have  recovered  withoul  the 
serum.  Several  others,  however,  presented  symptoms  of  extreme 
gravity;  one,  among  others  whom  Prof.  Pinard  was  called  to 
was  pronounced  to  be  in  a  hopeless  state.  In  order  to  obtain  thera- 
peutic effects,  considerable  doses  of  the  serum  musi  be  employed: 
the  introduction  of  60  C.cm.  per  day  •'!()  in  the  morning  and  .';<)  in 
the  evening.  In  one  case  we  injected  without  any  inconvenience 
300  c.cm.  in  four  clays.  The  patient,  who  was  comatose  at  the 
moment  of  intervention,  recovered  and  was  seen  by  us  ten  months 
later.  She  presented  no  disturbance  in  consequence  of  this  active 
treatment.  The  effects  of  the  serum  are  observed  in  the  local  lesione 
as  well  as  in  the  general  condition  of  the  patient.  Locally,  the  vulval 
wound  modifies,  the  congestion  disappears,  and  the  wound  assumes 
a  good  aspect.  In  one  case  the  pseudomembranes  which  covered 
the  vulva  and  vagina,  and  were  quite  intimately  adherent  to  the 
mucous  membrane,  were  easily  detached,  exactly  as  when  anti- 
diphtheritic  serum  is  injected  in  cases  of  anginas.  At  the  same 
time  the  general  state  is  improved,  the  patients  experience  a  feeling 
of  exhilaration,  and  the  skin  becomes  moist.  The  modifications  in 
the  temperature  are  quite  variable.  In  some  instances  fever  was 
not  influenced.  In  other  cases  it  fell  gradually  or  abruptly.  In  all 
the  successful  cases,  convalescence,  which  is  usually  so  long  after 
puerperal  fever,  was  remarkably  shortened. 

We  may  conclude  from  our  personal  observations  that  antistrepto- 
coccic serum  is  a  useful  auxiliary  in  the  treatment  of  puerperal  fever. 
We  believe,  however,  that  it  should  not  be  employed  to  the  exclusion 
of  all  other  therapeutic  measures:  and  we  do  not  accept  this  mode 
of  action  with  reference  to  diphtheria  in  which  it  is  far  more  justifi- 
able. We  think  that  all  measures  of  treatment  should  be  utilized, 
and,  according  to  the  cases  and  the  indications  of  each,  curettage 


720  INFECTIOUS  DISEASES. 

may  be  employed,  which  may  remove  placental  fragments  often 
filled  with  microbes  of  all  descriptions,  as  well  as  intra-uterine 
irrigations,  gastrointestinal  antisepsis,  and,  above  all,  cold  baths. 
Observations  taken  under  these  conditions  would  necessarily  be 
less  clearly  demonstrated  and  more  complex;  but  what  we  must 
look  for  is  not  the  demonstration  of  the  efficacy  of  a  method  at  the 
risk  of  the  patients'  lives.  It  would  not  be  right  to  make  such 
experiments.  Our  duty  is  to  benefit  those  under  our  care  by  all 
therapeutic  means  at  our  disposal.  In  order  to  obtain  results  from 
the  serum  we  must  not  wait  until  the  last  moment.  On  the  con- 
trary, we  should  intervene  from  the  very  beginning  of  manifestations, 
and  inject  large  doses,  and  combine  serumtherapy  with  the  other 
methods  of  treatment.  Such  is,  in  our  opinion,  the  line  of  conduct 
to  be  followed  in  the  presence  of  puerperal  fever,  or  rather  of  a 
puerperal  woman  suffering  from  fever.  It  is  hardly  necessary  to 
say  that  even  under  these  conditions  we  cannot  save  every  patient, 
and  this  for  several  reasons:  puerperal  fever  is  not  always  due 
to  the  streptococcus.  It  often  depends  upon  bacterial  association. 
Besides  the  streptococcus,  there  may  be  found  the  staphylococcus, 
the  pneumococcus,  the  pneumobacillus,  the  colon  bacillus,  the  septic 
vibrio,  etc.  Nevertheless,  the  serum  seems  to  be  efficacious  against 
at  least  one  of  these  microbes;  that  is,  the  pneumobacillus.  We 
have  observed  three  instances  of  this  kind. 

One  of  them  concerned  a  woman  who  had  an  attack  of  very 
grave  puerperal  fever.  The  symptoms  rapidly  yielded  after  two 
injections  of  the  serum,  30  c.cm.  each.  Examination  of  the  lochia 
did  not  reveal  any  other  microbes  than  the  pneumobacillus. 
The  second  case  was  that  of  a  puerperal  woman,  in  the  lochia  of 
whom  both  streptococcus  and  pneumobacillus  were  found.  One 
injection  sufficed  to  overcome  all  the  disquieting  symptoms. 
The  last  instance  concerned  a  woman  suffering  from  a  suppurative 
salpingitis,  upon  whom  laparotomy  was  practised  and  the  tubes 
were  extirpated.  During  the  operation  the  tubal  abscess  burst  and 
the  pus  spread  into  the  peritoneum.  Septicemic  phenomena  devel- 
oped, and  on  the  following  day,  the  patient  being  in  a  very  serious 
condition,  antistreptococcic  serum  was  injected  into  her.  In  four 
days  the  manifestations  subsided.  Examination  of  the  pus  revealed 
the  presence  of  the  pneumobacillus  alone. 

The  cultures  obtained  from  this  last  case  were  highly  virulent. 
One  cubic  centimetre  when  injected   into  the  veins  caused   death 


THEBAPEXJTI08  OF  INFECTIOUS  DISEASES.  721 

in  rabbits  within  twenty  four  or  thirty  is  hour  .  Pour  or  five  cubic 
centimetres  of  antistreptococcic  serum,  injected  al  the  Bame  time 
that  the  inoculation  was  made,  sufficed  to  save  the  animals.  The 
dose  may  seem  too  high,  Tins  experimental  result,  however,  i 
entirely  in  harmony  with  clinical  observations.  Still,  it  U  nol  to  be 
concluded  that  antistreptococcic  serum  is  efficacioui  against  the 
pneumobacillus.  M  was  such  againsl  these  samples,  and  even  in 
the  three  cases  if  acted  far  more  rapidly  and  energetically  than 
when  we  employed  it  in  infections  due  to  the  streptococcus. 

Our  last  observation  lends  us  to  say  a  word  regarding  the  employ- 
ment of  the  serum  in  surgical  septicemias.  The  rules  are  the  same 
us  in  puerperal  fever.  The  results  which  we  obtained  were  very 
satisfactory.  The  serum  was  tried  in  three  cases,  and  all  recovered. 
Marmorek  also  obtained  successful  results  under  the  same  conditions. 

The  .serum  has  not  yet  been  used  in  cases  of  diffuse  phlegmons 
or  streptococcic  suppuration.  It  is  not  likely  thai  it  would  prove 
efficacious.  Likewise,  we  know  very  little  as  to  its  role  in  cases  of 
bronchopneumonia.  A  few  attempts  were  made  in  scarlatina  by 
Marmorek,  Josias,  and  Baginsky.  The  results  were  quite  uncertain, 
which  is  not  to  be  wondered  at,  since  it  is  not  known  what  role  is 
played  by  the  streptococcus  in  scarlatinal  manifestations,  even  in 
the  anginas. 

We  have  expounded  at  some  length  upon  antistreptococcic  serum- 
therapy,  because  a  future  seems  to  be  reserved  for  this  method. 
No  doubt  the  results  are  not  yet  perfect.  They  will  be  better  when 
more  active  serums  are  obtained,  and  particularly  when  the  treat- 
ment is  instituted  from  the  very  start  of  the  morbid  manifestations. 
It  is  evident  that  success  is  not  to  be  expected  in  every  case,  since 
the  infections  are  sometimes  mixed,  and  the  serum  cannot  be  effi- 
cacious against  all  the  streptococci.  An  animal  which  is  immunized 
against  one  variety,  furnishes  a  serum  that  is  powerless  against  the 
other  varieties.  It  is  well,  therefore,  to  immunize  animals  by  inject- 
ing cultures  obtained  from  various  sources.  Such  is  the  method  at 
present  employed  by  Denys.  Lastly,  as  regards  puerperal  infection, 
we  must  take  into  consideration  the  role  of  the  living  microbes  and 
that  of  the  bacterial  toxins.  Numerous  examples,  notably  the  study 
of  cholera  cases,  show  that,  according  to  the  procedures  of  immuniza- 
tion, the  animals  furnish  either  germicidal  or  antitoxic  serums,  that 
is  to  say,  sera  acting  upon  the  living  microbes  or  upon  their  secre- 
tions.   Hence,  it  is  necessary  to  prepare  serums  endowed  with  both 

46 


722  INFECTIOUS  DISEASES. 

of  i hose  properties,  so  that  the  antitoxin  may  combat  the  action  of 
harmful  products  already  diffused  in  the  organism,  while  the  anti- 
bacterial substance  hinders  the  further  development  of  the  figurate 
elements. 

Tetanus.  Antitetanic  serum  is  also  the  work  of  Behring  and 
Kitasato.  .Those  authors  discovered  the  means  of  immunizing 
against  the  microbe.  They  succeeded  with  toxins  treated  with 
trichloride  of  iodine  or  cultures  prepared  in  thymus  gland  bouillon. 
Immunity  was  subsequently  obtained  by  other  procedures  as  well. 
Vaillard  employed  filtered  cultures  which  were  attenuated  by  heat 
between  122°  and  140°  F.  (50°  and  60°  C).  Roux  and  Vaillard 
employed,  as  in  diphtheria,  a  mixture  with  iodized  water.. 

The  serum  of  vaccinated  animals  was  first  studied  by  Behring 
and  Kitasato,  who  recognized  that  it  possessed  the  same  property 
as  the  antidiphtheritic  serum.  It  neutralizes  poisons — i.  e.,  it  is 
antitoxin.  This  result  immediately  led  to  therapeutic  investigations, 
since,  as  is  known,  tetanus  is  one  of  the  infectious  diseases  in  which 
intoxication  plays  the  principal  role.  The  results  obtained  by 
Behring  and  Kitasato  at  first  appeared  very  encouraging.  These 
authors  declared  that  antitetanic  serum  protects  the  animal  into 
which  it  is  injected  against  tetanus,  and  may  even  cure  the  estab- 
lished disease.  They  asserted  that  it  was  possible  to  save  a  mouse 
already  presenting  the  characteristic  contractures. 

These  experiments,  however,  were  controlled  by  Tizzoni  and 
Cattani,  Vaillard,  and  then  by  Kitasato  himself,  but  gave  negative 
results  from  a  therapeutic  standpoint.  Roux  and  Vaillard  subse- 
quently proved  that  the  serum,  when  injected  before  inoculation, 
protects  the  animals.  When  it  is  introduced  coincidently  with  the 
toxin  or  a  little  later,  it  attenuates  the  manifestations  and  permits 
only  a  local  tetanus.  But  it  is  absolutely  inefficient  when  injected 
into  animals  already  presenting  contractures. 

This  last  result  raises  a  theoretical  question  of  considerable 
interest.  The  inefficiency  of  the  serum  is  not  well  understood  if 
it  is  admitted  that  the  antitoxin  neutralizes  the  toxin.  On  the 
other  hand,  if  it  is  supposed — and  this  is  the  prevailing  theory — 
that  antitoxins  act  by  increasing  the  resistance  of  the  anatomical 
elements,  perhaps  by  preventing  their  impregnation,  it  is  then  con- 
ceivable that  injection  of  the  serum  will  not  suffice  to  arrest  the 
evolution  of  the  disease.  Sahli,  whose  theory  is  similar  to  that 
advanced  by  Courmont  and    Doyon  (p.  413),  goes  further.      He 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  723 

believes  that  the  toxins  are  often  eliminated  when  the  manifestations 
appear,  but  that  they  leave  in  thenervou  j  tem  alteration  which 
follow  an  independent  course  The  serum  does  not  act  upon  these 
lesions  any  more  than  the  salicylate  does  upon  rheumatic  endo- 
carditis. 

The  serum  is  employed  rather  as  a  preventive,  h  i  employed 
for  man  when  a  wound  is  contaminated  by  soil,  particularly  in 
countries  where  tetanus  is  frequent  or  in  individual  who  come  in 
contact  with  horses.  In  veterinary  medicine  ii  renders  aum< 
services.  It  is  often  injected  us  a  prophylactic  into  horsee  which 
arc  about  to  be  castrated. 

The  serum  is  still  administered  to  man  in  subcutaneous  injections, 
and  in  largo  doses  in  cases  of  established  tetanus.  Suca 
recorded  from  time  to  time.  Several  such  observations,  however, 
are  liable  to  crilicisni.  It  has,  therefore,  been  thought  thai  the 
mode  of  introduction  of  the  serum  required  some  modification. 
As  a  result  of  their  investigations  on  cerebral  tetanus,  Rous  and 
Borrel  conceived  the  idea  of  injecting  the  serum  directly  into  the 
cerebral  substance  of  tetanic  patients.  Experiments  pursued  upon 
animals  seemed  to  demonstrate  the  value  of  the  method. 

The  first  application  to  man  was  made  by  Chauffard  and  Quenu. 
The  patient  recovered.  Two  months  later,  Gamier  published  the 
report  of  a  successful  case  observed  in  our  wards.  It  was  a  case 
characterized  by  a  slow  course.  During  the  first  three  days  the 
tetanus  was  benign.  The  fourth  day,  the  state  being  aggravated, 
we  decided  to  intervene.  Six  cubic  centimetres  of  concentrated 
serum,  equivalent  to  15  corn,  of  the  ordinary  serum,  were  injected 
into  the  two  cerebral  hemispheres.  Simultaneously  116  c.cm.  were 
injected  beneath  the  skin.  At  the  end  of  three  days  amelioration 
was  manifest.  Recovery  was  complete  a  month  later.  Conval- 
escence was  disturbed  by  psychic  disorders  and  erotic  delirium. 
These  phenomena  were  transitory.  By  collecting  the  published 
observations,  a  death-rate  of  75  per  cent,  was  found:  that  is 
larger  than  the  average  death-rate,  which  does  not  exceed  70  per 
cent.  As  nothing  regarding  this  method  has  been  published  for 
some  time,  it  may  be  supposed  that  it  has  been  almost  abandoned. 
Is  it  at  least  inoffensive?  The  majority  of  authors  suppose  it  to  be 
so.  In  the  case  of  Gamier,  however,  psychic  disorders,  though  of 
a  transitory  character,  developed  in  consequence  of  the  injection. 
In  another  case  observed  by  us  and  published  by  Dr.  Robert,  death 


724  INFECTIOUS  DISEASES. 

occurred  twenty-four  hours  after  the  injection.  The  necropsy  re- 
vealed acute  edema  of  the  meninges  and,  in  one  of  the  cerebral  lobes, 
a  cavity  filled  with  a  sanguinolent  fluid.  It  may  well  be  asked 
whether  such  a  lesion  in  so  delicate  an  organ  may  be  considered 
indifferent. 

Instead  of  introducing  the  serum  into  the  brain,  Sicard  injected 
it  into  the  lumbar  subarachnoidal  cavity.  The  results  obtained  in 
dogs  were  very  encouraging.  In  man  the  method  does  not  seem 
to  have  been  successful.  Thus  we  find,  with  reference  to  tetanus, 
the  antagonism  which  we  noted  on  several  occasions  between  the 
results  obtained  in  laboratories  and  facts  of  clinical  observation. 
This  does  not  mean  that  the  importance  of  experimental  investiga- 
tions is  any  less  valuable;  but  it  should  be  recognized  that  human 
pathology  is  extremely  complex,  and,  therefore,  it  is  necessary  to 
pursue  new  researches  and  make  new  attempts. 

Tuberculosis.  Richet  and  Hericourt1  were  the  first  to  attempt 
antitubercular  serumtherapy  by  injecting  the  blood  of  dogs  into 
the  peritoneum  of  rabbits  inoculated  with  cultures  of  avian  or 
bovine  tuberculosis.  The  quantity  of  blood  transfused  varied  from 
16  to  41  grams.  The  mortality  of  the  controls  was  55  per  cent., 
and  that  of  the  transfused  17  per  cent.  Soon  after,  Bertin  and  Picq 
made  analogous  attempts  with  the  blood  of  goats,  which  are  reputed 
to  be  immune  to  tuberculosis.  By  employing  2.5  grams  per  kilogram 
of  animal  they  succeeded  in  preventing  or  arresting  the  develop- 
ment of  the  disease. 

These  results  were  soon  applied  clinically,  and  a  few  successes  seem 
to  have  been  obtained  by  subcutaneous  injections  of  the  blood  of 
dogs  and  goats.  In  spite  of  these  encouraging  results,  the  employ- 
ment of  the  blood  of  normal  animals  did  not  lead  to  a  definitive 
method.  The  serum  of  naturally  immune  animals  almost  never 
possesses  true  curative  power,  for  the  reason  that  natural  immunity 
is  always  contingent  and  is  never  absolute.  In  regard  to  tuberculosis, 
this  law  is  the  more  accurate,  as  we  know  of  no  mammalian  that  is 
endowed  with  a  notable  resistance.  The  serum  of  the  gallina3,  the 
only  animals  enjoying  a  certain  immunity,  does  not  possess  the 
power  of  arresting  the  evolution  of  tuberculosis  in  mammalia  into 
which  it  is  injected.  Extracts  of  the  organs  have  not  proved  to  be 
any  more  efficacious. 

1  Hericourt  and  Richet.  Influence  de  la  transfusion  pe>iton6ale  du  sang  de  chien  sur 
Involution  de  la  tuberculose  chez  le  lapin.     Society  de  biologie,  March  2,  1889. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  725 

Experimenters  were,  therefore,  led  to  investigate  whether  it 
possible,  l>y  various  procedures,  to  confer  artificial  therapeutic 
power  upon  the  serum  of  certain  animals.  A  good  many  attempts 
were,  made  in  this  direction.  In  spile  of  their  apparenl  multiplicity, 
the  procedures  employed  are  divisible  into  three  groups:  I .  Employ- 
ment of  living  cultures.  2.  Employmenl  of  iterilized  cult 
3.  Mixed  method,  in  which  both  soluble  products  and  living  culture* 
are  made  use  of. 

1.  The  Serum  of  Animals  Treatedwith  Living  Cultures.  This  pro- 
cedure was  variously  u1  ilized.  I  [ericourl  and  Richel ,  having  obtained 
a  relative  immunity  in  dogs  which  had  received  avian  tuberculosis, 
were  naturally  led  to  study  the  therapeutic  action  of  their  Quids. 
They  employed  the  serum  obtained  by  modulating  avian  tubercu- 
losis beneath  the  skin  of  the  dog.  This  fluid,  which  the  authors 
called  phymoserum,  when  freed  from  leucocytes,  is  found  to  po 
well-marked  immunizing  properties  with  regard  to  rabbits.  The 
authors,  however,  seem  to  have  abandoned  this  method  in  order  to 
prepare  a  neoserum  with  animals  inoculated  with  human  tubercu- 
losis. 

The  procedure  of  Hericourt  and  Richet  consists  in  inoculating  with 
human  tuberculosis  animals  of  slight  susceptibility,  such  as  asses  and 
dogs.  In  a  first  series  of  experiments  the  serum  was  furnished  by 
an  ass  which  received,  one  month  previously,  an  injection  of  virulent 
human  tuberculosis.  AVhile  the  control  guinea-pigs  died  at  the  end 
of  two  months,  out  of  four  guinea-pigs  treated,  two  were  still  living 
at  the  end  of  seventy-one  clays.  In  another  note  the  authors  an- 
nounced that  they  had  inoculated  dogs  with  tubercle  bacilli  pre- 
viously freed  from  tuberculin  by  washing.  The  inoculations  were 
made  into  the  veins,  and  the  animals  were  bled  at  the  end  of  ten 
days.  The  serum  was  used  to  treat  a  woman,  thirty-four  years  of 
age,  in  whom  a  very  manifest  amelioration  was  observed.  A  few 
months  later  Redon  and  Chenot  announced  that  it  was  possible  to 
prevent  tuberculosis  in  rabbits  and  guinea-pigs  by  injecting  into 
them  the  serum  of  asses  or  mules  which  had  previously  been  inocu- 
lated with  tuberculosis  and  presented  no  lesion  in  consequence  of 
this  operation.  The  results  were  still  better  when  the  serum  of  horses 
first  treated  with  tannin  was  used  than  when  active  tubercular  virus 
was  employed. 

Evidently  here  are  very  interesting  results  which  are.  nevertheless, 
open  to  criticism.    The  dog,  the  ass,  the  mule,  and  the  horse  are  far 


726  IXFECTIOUS  DISEASES. 

from  presenting  a  natural  resistance  as  pronounced  as  was  once 
believed.  In  those  cases  in  which  dogs  and  goats  withstood  virulent 
inoculations  and  in  those  instances  in  which  animals  of  this  same 
species  presented  only  very  discrete  lesions,  Silvestrini  obtained  no 
notable  effect  by  treating  tubercular  guinea-pigs  with  their  sera. 
With  Cadiot  we  tried,  with  no  greater  success,  the  serum  of  an  ass 
which  presented  a  voluminous  local  lesion  produced  by  inocu- 
lation of  human  tuberculosis.  The  guinea-pigs  which  received  the 
serum  died  more  rapidly  than  the  controls.  On  the  other  hand, 
Broca  and  Charrin  obtained  encouraging  results  in  man.  The  serum 
employed  was  that  of  dogs  suffering  from  a  local  tubercular  lesion. 
The  injections,  when  made  into  patients  affected  with  lupus  or 
fungous  ulcerations  consecutive  to  incomplete  surgical  intervention, 
produced  notable  amelioration  in  the  lesions. 

How  are  these  favorable  results  to  be  explained?  Can  it  be 
assumed  that  the  serum  acted  simply  like  the  normal  serum  of  the 
dog,  which  also  possesses  the  power  of  improving  cutaneous  tuber- 
culosis (Feulard)?  This  interpretation  is  inadmissible.  It  is  well, 
however,  to  take  into  account  the  possibility  of  an  action  comparable 
to  that  of  tuberculin.  In  fact,  it  seems  that  in  the  course  of  tuber- 
culosis the  blood  contains  a  substance  analogous  to  that  extracted 
by  Koch  from  cultures  of  his  bacillus.  The  blood  of  tubercular  dogs 
possibly  represents  a  dilution  of  tuberculin  which  is  too  weak  to 
give  rise  to  dangerous  reactions,  but  sufficient  to  ameliorate  local 
lesions.  This  explanation  seems  to  me  the  more  admissible,  since 
Koch's  lymph  is  most  efficient  in  lupus  and  external  tuberculosis. 

While  virulent  cultures  do  not  seem  to  yield  good  results,  it  may 
be  hoped  that  attenuated  cultures  will  prove  more  satisfactory. 
Researches  published  by  Schweinitz  and  Dorset  tend  to  prove  this. 
Two  horses  received  considerable  quantities  of  attenuated  cultures 
— as  much  as  4590  c.cm.  in  eight  months.  The  serum  of  the  animals 
thus  treated  possessed  the  power  of  prolonging  the  life  of  tubercular 
guinea-pigs  and  even  of  saving  some  of  them. 

2.  Serum  of  Animals  Treated  with  Sterilized  Cultures,  Extracts, 
Tuberculin,  etc.  In  view  of  the  principle  that  the  presence  of  a  poison 
causes  the  elaboration  of  an  antitoxin  in  the  organism,  it  was  natural 
to  investigate  what  would  happen  in  animals  as  a  result  of  injection 
of  tubercular  poison,  notably  tuberculin.  Hericourt  and  Richet 
experimented  with  the  serum  and  milk  of  female  asses  which  had 
previously  been  injected  with  Koch's  lymph.    The  animals  treated 


THERAPEUTICS  OF  INFECTIOUS  DI8EASES.  727 

with  these  products  succumbed  more  rapidly  than  the  controls.  A 
few  months  later,  Dr.  Boinel  announced  thai  the  erum  of  tubercu- 
linized  goats  protected  guinea  -pigs  into  which  an  inoculation  of  viru- 
lent tuberculosis  was  afterward  made.  When  employed  inpatients 
the  serum  produced  amelioration  in  mild  forms  of  tuberculoses,  bul 
it  was  ineffective  in  individuals  with  cavities  and  in  those  presenting 
febrile  movements  or  hemoptysis. 

The  presence  of  an  antituberculin  in  the  blood  of  animals  treated 
with  tuberculin  was  proved  especially  by  the  investigation*  of  Behr- 
ing  and  of  Niemann.  I'ehring,  in  collaboration  with  Wernicke  and 
Knorr,  found  antifuberculin  in  the  blood  of  man  and  animals  which 
had  been  injected  with  progressively  increasing  amounts  of  tuber- 
culin. In  order  to  demonstrate  Ibis  these  authors  injected  fatal  doses 
of  tuberculin  into  tubercular  guinea-pigs.  Those  animals  which 
received  the  scrum  at  the  same  time  the  tuberculin  was  injected  did 
not  die.  Niemann  published  analogous  experiments.  He  resorted 
to  very  different  animals — dogs,  goats,  guinea-pigs,  white  rats,  por- 
cupines— and  injected  into  them  progressively  increased  doses  of 
tuberculin,  or,  still  better,  a  precipitate  obtained  by  mean-  of  alcohol, 
so  as  to  free  it  from  glycerin.  He  thus  conferred  upon  them  a  certain 
immunity  against  virulent  inoculations.  He  then  tried  the  serum 
upon  tubercular  guinea-pigs,  with  the  following  results:  40  eg.  of 
tuberculin  killed  the  animals  in  a  period  of  time  varying  from  four- 
teen to  seventeen  hours.  The  same  dose,  when  mixed  with  8  c.cm. 
of  the  serum  killed  the  animals  in  twenty  or  thirty  hours.  "With 
10  c.cm.  the  animals  lived  twenty-two  days,  and  with  12  c.cm.  from 
thirty-five  to  forty-two  days.  Finally,  6  grams  of  serum  of  a  goat 
which  had  received  tuberculin  and  dead  bacilli  preserved  the  lives 
of  the  animals  for  from  fifty  to  seventy  days. 

Maffucci  and  Di  Vestea  injected  into  sheep  456  mg.  to  1670  mg. 
of  bacilli  killed  by  exposure  to  a  temperature  of  230°  F.  (110°  C.) 
for  twenty  minutes.  Living  bacilli  placed  in  contact  for  half  an  hour 
with  the  serum  taken  from  these  animals  lost  part  of  their  virulence. 
Guinea-pigs  which  were  inoculated  with  the  mixture  died  far  mure 
slowty  than  those  which  received  only  the  bacilli  or  those  which 
received  the  bacilli  and  the  serum  separately.  The  latter,  how- 
ever, survived  a  little  longer  than  the  controls.  It  would  seem, 
therefore,  that  under  the  influence  of  tubercular  products  there  is 
formed  in  the  organism  a  substance  possessing  the  power  of  at- 
tenuating the  action  of   tubercular  toxins  and  even  of   the  living 


728  IXFECTIO  US  DISEA SES. 

bacilli.    In  the  latter  ease  the  two  products  must  be  previously  mixed 
in  vitreo. 

3.  Mixed  Method.  As  early  as  1892  Babes  and  Broca  conceived 
the  idea  of  preparing  animals  by  means  of  injections  of  avian  and 
human  tuberculin,  then  by  inoculating  into  them  avian  tuberculosis, 
and,  lastly,  human  tuberculosis.  The  blood  and  the  serum  taken 
from  dogs,  rabbits,  guinea-pigs,  and  cows  treated  in  this  manner 
neutralized  tuberculin  and  prevented  or  cured  tuberculosis  in  rabbits 
and  guinea-pigs.  The  employment  of  these  fluids  produced  good 
results,  even  in  man;  the  fever  ceased,  the  weight  increased,  and  the 
cutaneous  lesions,  notably  lupus,  improved. 

Antitubercular  Serumtherapy  in  Man;  the  Serum  of  Maragliano. 
As  has  already  been  stated,  several  authors  had  obtained  in  man 
more  or  less  marked  improvements.  Hericourt  and  Richet,  as  well 
as  Boinet,  utilized  the  serum  of  animals  the  resistance  of  which  they 
thought  they  had  increased.  Paquin  prepared  a  serum  of  equine 
origin.  Bloch  advocated  the  employment  of  the  blood  taken  from 
the  subcutaneous  capillary  network.  The  investigations  of  Marag- 
liano placed  the  question  upon  a  practical  basis.  In  the  first  place 
this  author  established  that  tubercular  cultures  contained  two  kinds 
of  toxic  substances.  Some  of  them,  which  are  obtained  by  concen- 
trating the  culture  at  212°  F.  (100°  C),  are  represented  by  proteins 
derived  from  the  bodies  of  the  bacilli.  These  are  the  substances 
found  in  Koch's  lymph.  The  others,  which  are  prepared  by  concen- 
trating in  vacuo  at  86°  F.  (30°  C.)  and  filtering  the  culture  through 
porcelain,  are  particularly  toxalbumins.  This  latter  fluid  manifests 
an  action  altogether  opposite  to  that  of  the  former.  It  kills  the 
animals  in  a  state  of  collapse,  while  tuberculin  produces  hyper- 
thermia. 

The  animals  which  furnish  the  serum — goats,  asses,  and  horses — 
are  injected  with  progressively  increasing  doses  of  a  mixture  of  three 
parts  of  the  former  and  one  part  of  the  latter  fluid.  At  the  end  of 
six  months  immunization  is  obtained,  and  three  or  four  weeks  after 
the  last  injection,  venesection  is  practised.  The  serum  is  germicidal 
as  well  as  antitoxic.  It  annihilates  the  toxic  action  of  tuberculin. 
In  a  normal  guinea-pig  1  gram  of  the  serum  neutralizes  a  fatal  dose 
of  tuberculin.  In  tubercular  guinea-pigs,  which  succumb  to  a  ten 
times  smaller  dose  of  tuberculin,  it  is  necessary  to  inject  2  to  4  grams 
of  the  serum  per  kilogram  of  animal  in  order  to  save  them.  As 
regards  tubercular  human  subjects,  the  dose  of  tuberculin  which 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8ES.  12'.) 

causes  fever  is  neutralized  by  I  c.cm.  of  the  serum.  After  they  have 
I )fcn  treated  l>y  the  serum  the  tuberculous  individual  become  in  en- 
sible  to  IIk'  action  of  tuberculin,  even  when  use  i  made  of  'I''  e  ten 
times  larger  than  those  which,  ;ii  Hi''  beginning,  gave  rise  to  reaction* . 
The  treatment  consists  in  injecting  into  the  patienl  I  c.cm.  every 
other  day.  In  febrile  cases  in  which  no  reduction  in  the  temperature 
is  obtained,  the  doses  are  increased  t<>  5  c.cm.  and  10  c.cm.  If  the 
fever  disappears  the  dose  is  again  reduced  to  I  c.cm.  This  dose  i- 
to  be  employed  if  the  febrile  process  is  not  arrested  by  higher  d< 
This  treatment  should  be  stopped  in  case  of  hemoptysis.  A  greal 
number  of  physicians  made  use  of  Maragliano's  serum,  and  the  obser- 
vations published  are  quite  favorable  to  the  method.  The  serum 
proved  useful  in  01  per  cent,  of  the  cases,  and  it  proved  curative  in 
1G  per  cent . 

It  is  evidently  too  soon  to  conclude  Hint  Marnglinno's  serum  is  the 
true  specific  of  tuberculosis.  Numerous  negative  facts  do  not  permit 
such  optimism.  The  fact  that  may  at  once  be  recognized  is  that  the 
medicine  when  employed  in  amounts  indicated  by  the  author  does 
not  seem  to  be  dangerous  and  is  at  times  efficacious.  Perhaps  the 
failures  are  due  in  part  to  the  fact  that  in  man  the  process  is  always 
complex.  Besides  tuberculosis,  a  whole  series  of  secondary  infect  ions 
are  to  be  combated.  Here  is  the  stumbling-block  of  antitubercular 
serumtherapy.  The  day  we  possess  a  serum  capable  of  combating 
or  destroying  Koch's  bacillus  we  shall  still  lack  an  infallible  serum 
against  tuberculosis,  for,  barring  the  cases  of  acute  miliary  tubercu- 
losis, the  infection  is  mixed,  and,  when  it  has  reached  the  third  stage, 
the  patient  that  has  pulmonary  cavities  and  is  suffering  from  hectic 
fever  is  a  pyohemic  rather  than  a  bacillary  sufferer.  A  whole  series 
of  serums,  varying  from  one  case  to  another,  must  be  employed  in 
a  polymicrobic  infection.  The  impossibility  if  not  the  dangerous 
character  of  such  therapeutics  is  evident. 

Typhoid  Fever.  It  is  not  difficult  to  vaccinate  animals  against  the 
bacillus  of  Eberth.  This  may  be  accomplished  by  employing  the 
living  microbes,  as  has  been  done  by  Beumer  and  Peiper,  or  by 
making  use  of  sterilized  cultures,  as  was  advised  by  Chantemesse  and 
Widal,  Brieger,  Kitasato,  and  Wassermann.  The  majority  of  authors 
to-day  resort  to  the  latter  method.  In  order,  however,  to  obtain  an 
active  serum,  an  exalted  virus  must  be  employed.  The  best  means 
consists  in  making  passages  in  series  on  animals,  by  favoring  the 
development  of  the  pathogenic  agent  by  means  of  simultaneous  injec- 


730  I -v I'ECTIO US  DISEA SES. 

tions  of  microbic  toxins.  These  toxins  are  of  two  orders.  Some  are 
contained  in  the  bodies  of  microbes.  Funck  makes  use  of  these  for 
immunizing  animals.  On  the  other  hand,  Chantemesse  utilizes  the 
poisons  fchat  diffuse  into  the  culture  bouillon.  By  means  of  a  special 
mi',  lium  he  obtains  a  very  active  toxin  which  enables  him  to  immun- 
ize horses,  but  the  experiment  is  extremely  long.  It  was  only  after 
two  years  of  preparation  that  Chantemesse  obtained  a  truly  active 
serum.  Klempcrer  and  Levy,  with  the  serum  of  dogs,  and  Borge, 
with  a  serum  of  sheep  prepared  by  Beumer  and  Peiper,  succeeded  in 
shortening  the  morbid  evolution. 

Chantemesse,  after  establishing  the  immunizing  and  curative  power 
of  this  serum  upon  animals,  obtained  very  encouraging  results  in 
man.  One-fiftieth  of  a  cubic  centimetre  of  the  serum  injected  as  a 
prophylactic  into  a  guinea-pig  confers  immunity  against  a  fatal  dose 
of  toxin.  When  he  injected  into  guinea-pigs  a  dose  of  toxin  which 
killed  the  controls  in  twenty-four  or  forty-eight  hours,  the  guinea-pigs 
which  subsequently  received  25  eg.  of  serum  four  and  even  five  hours 
after  introduction  of  the  poison  usually  resisted. 

In  man  the  treatment  reduced  the  mortality  to  less  than  6  per 
cent.  The  study  of  observations  and  of  the  course  of  the  fever 
demonstrates  the  efficiency  of  the  method  more  than  statistics.  An 
injection  of  from  10  c.cm.  to  20  c.cm.  of  serum  suffices  to  lower  the 
temperature  and  cause  the  diazo  reaction  to  disappear.  The  duration 
of  the  disease  is  shortened.  Defervescence  occurs  early,  and,  contrary 
to  what  usually  happens,  the  urine  remains  scanty  for  several  days 
after  the  fall  of  the  fever. 

Infections  the  Agents  of  Which  are  Unknown  or  Not  Well  Known. 
We  place  in  a  separate  group  those  infectious  diseases  the  microbes 
of  which  are  unknown,  or  little  known,  or  have  not  been  cultivated. 
Numerous  attempts  have  been  made  in  such  cases,  by  employing 
the  blood  and  the  serum  of  convalescent  men  or  of  animals  into 
which  virulent  products  obtained  from  man  had  been  injected. 

Eruptive  Fevers.  The  eruptive  fevers,  such  as  measles  and  scarla- 
tina, are  not  transmissible  to  animals.  Kelaidites  injected  into 
heifers  the  blood  and  squamae  of  scarlatinal  patients.  From  20  c.cm. 
to  30  c.cm.  of  the  serum  of  animals  thus  treated  sufficed  to  arrest 
the  course  of  the  infection.  The  same  author  prepared  a  serum 
against  whooping-cough  by  injecting  into  dogs  the  bronchial  and 
nasal  secretions  of  patients.  In  most  cases  the  serum  of  convales- 
cents was  made  use  of  for  therapeutic  purposes.    This  is  what  we 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  7:; I 

accomplished  in  several  cases  of  scarlatina.  The  method  is  quite 
simple  and  appears  to  be  efficacious,  as  may  be  judged  from  the 
following  observal  ion :' 

At  8  p.m.  on  June  17,  L896,  a  young  man,  fifteen  year  ol  age, 
was  brought  fco  our  wards  suffering  from  scarlatina.  The  attach 
had  taken  place  forty-eight  hours  previoui  ly  and  had  been  ushered 
in  by  vertigo,  headache,  and  sore  throat.  At  the  time  of  bU  admis 
sion  we  were  struck  by  the  gravity  of  the  general  Btate.  The 
patient  was  motionless  and  semicomatose.  From  time  to  time 
his  limbs  were  shaken  by  slight  convulsive  movements,  his  face 
drawn,  his  eyes  fixed,  and  dyspnea  whs  extremely  intense.  S 
eight  respiratory  movements  ;i,  niinule  were  count  c<\  ;md  l_'0  regular 
and  quite  strong  heart-boats.  The.  skin  \v;is  covered  with  ;i  general- 
ized scarlatinal  erupt  ion.  The  tongue  was  dry  and  the  tonsilfl  swollen 
and  covered  with  a  pultaceous  deposit.  After  his  arrival  the  patienl 
voided  a  small  amount  of  non-albuminous  urine.  Owing  to  the 
gravity  of  the  general  state  our  interne  gave,  at  10  p.m.,  a  subcu- 
taneous injection  of  400  grams  of  salt-water;  at  1  a.m.  a  bath  was 
given  at  82.4°  F.  (28°  C). 

On  the  morning  of  the  18th  the  general  state  was  about  the  same 
as  on  the  previous  evening.  The  patient  was  comatose,  and  his 
extremities  were  at  times  convulsed,  the  tongue  dry,  the  tempera- 
ture, taken  every  three  hours,  was  reduced  after  the  administration 
of  the  bath,  then  it  rose  and,  in  the  morning,  reached  10.5.3°  F. 
(40.2°  C).  The  number  of  respirations  was  68;  the  pulse  did  not 
exceed  120,  but  was  extremely  weak.  The  patient  had  voided  no 
urine  since  the  previous  night. 

A  fatal  termination  seemed  to  be  approaching.  We  resolved  to 
employ  serum  treatment.  A  man  convalescent  from  scarlatina  was 
willing  to  furnish  the  blood.  As,  however,  it  was  necessary  to  act 
promptly,  we  could  not  prepare  serum.  Hence,  we  decided  to  inject 
defibrinated  blood.  For  this  purpose  we  took  a  glass  ball,  and.  after 
introducing  into  it  a  certain  quantity  of  pearls,  closed  it  with 
cotton.  The  ball  was  sterilized  at  356°  F.  (180°  C).  The  vein  of 
the  convalescent  was  then  opened  and  100  grams  of  blood  drawn. 
By  gently  agitating  the  ball  the  pearls  separated  the  fibrin,  and  an 
aseptic  fluid  was  thus  obtained.  These  preparations  had  taken  an 
horn.    During  this  time  the  state  of  the  young  man  had  become  still 

1  Roger.  Quelques  reflexions  sur  le  traitement  des  searlatines  graves.  Essai  de 
s£roth6rapie.     La  presse  medieale.  1S96. 


732  INFECTIO  US  DISEA  SES. 

worse,  and  a  fatal  issue  seemed  imminent.  At  11  a.m.  we  bled  the 
patient  and  took  from  him  150  grams  of  blood.  Eighty  cubic  centi- 
metres of  defibrinated  blood  taken  from  the  convalescent  were  then 
injected  beneath  the  skin  of  the  abdomen. 

At  4  p.m..  when  the  author  saw  the  patient,  he  found  him  sleeping 
and  breathing  quietly ;  he  then  awoke  and,  having  made  a  few  move- 
ments, the  respiratory  rhythm  changed  and  assumed  the  type  of 
Chcyne-Stokes.  The  pulse-beat  was  120  and  weak,  although  less  so 
than  in  the  morning.  Prostration  was  less  marked  and  the  tongue 
had  become  moist.  In  spite  of  this  notable  amelioration  of  the  gen- 
eral state,  the  temperature  remained  high  and  the  patient  passed  no 
urine.  He  was  then  given  a  bath  at  82.4°  F.  (28°  C).  The  tempera- 
ture then  began  to  fall.  At  7  p.m.  400  grams  of  salt  water  were 
injected  beneath  the  skin.  At  8  p.m.  he  passed  urine.  At  10  p.m. 
the  interne  found  the  patient  sleeping  quietly,  his  pulse  100,  respira- 
tions 25  per  minute.  On  the  following  morning  the  patient  was 
found  completely  transformed ;  he  spoke  easily,  felt  well,  and  asked 
for  food.  The  tongue  was  desquamated  but  moist,  and  the  eruption 
was  pale,  except  in  the  lower  extremities,  where  it  was  still  marked. 
The  pulse,  80  per  minute,  was  still  somewhat  weak,  but  very  regular, 
and  the  respiration  22.  Finally,  since  8  o'clock  of  the  previous  even- 
ing until  8  o'clock  the  next  morning,  the  patient  voided  1100  c.cm. 
of  a  dark  red,  non-albuminous  urine.  The  temperature  oscillated 
during  the  day  around  100.4°  F.  (38°  C),  and  on  the  following  day 
it  returned  to  the  normal  in  a  definitive  manner.  On  the  following 
days  nothing  special  was  noted.  The  infection  was  shortened,  and 
in  so  serious  a  case  we  have  never  seen  so  rapid  a  convalescence. 

When  recovered  the  patient  told  us  that  he  did  not  remember  his 
arrival  at  the  hospital  or  the  salt-water  injection  given  him  at 
that  time.  He  remembered  only  the  bath  which  had  been  given  at 
night.  This  consciousness,  however,  had  not  lasted  long,  for  the 
patient  could  not  recall  the  bleeding  nor  the  injection  of  defibrinated 
blood.  He  had  come  out  of  his  comatose  state  later  in  the  day.  He 
clearly  had  kept  the  remembrance  of  my  visit  of  4  p.m.  and  all  the 
events  taking  place  after  that  time.  These  retrospective  details  are 
interesting  inasmuch  as  they  show  the  extreme  gravity  of  the  situa- 
tion at  the  time  of  intervention.  It  may  be  said  that  our  observation 
is  too  complex,  since  recourse  was  had  simultaneously  to  several 
therapeutic  methods.  This  mode  of  action  renders  demonstrations 
less  exact,  but  it  was  the  only  one  permissible.     By  studying  the 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  i:',\', 

evolution  of  the  disease,  however,  it.  is  possible  to  di  cern  whal  U  due 
to  each  procedure  cm  ployed,  [mprovemenl  began  after  the  injection 
of  the  blood  and,  unless  it,  is  assumed  thai  the  change  in  the  general 
state  would  have  occurred  even  withoui  intervention,  which  is  among 
the  possible  events,  the  amelioration  is  to  be  attributed  to  the 
influence  of  the  hemotherapy.  The  improvemenl  thu  started  con- 
tinued, owing  to  the  auxiliary  action  of  the  bath  and  especially  to 
the  injection  of  salt-water. 

The  same  hemotherapic  method  is  applicable  to  measles.  In  f'»ur 
cases  Weisbee.ker  saw  rapid  arrest  of  bronchopneumonias  "I  measles 
under  the  influence  of  the  serum  of  convalescenl  individuals.  These 
researches  are  the  more  important  as  (hey  were  made  on  very  young 
children — i.  c,  under  particularly  grave  conditions.  The  rapid  dis- 
appearance of  the  thoracic  manifestations  leads  to  the  question 
whether  bronchopneumonia  is  really,  as  is  generally  admitted,  exclu- 
sively dependent  upon  secondary  infection,  or  whether, ,i~  hr.  I -'  -■■  ■  ir< • 
thinks,  the  principal  agent  of  the  disease  plays  a  more  important 
role  in  its  development  than  is  generally  supposed. 

Analogous  methods  have  been  employed  against  recurrent  fever, 
(Gabritchewski),  typhus  fever  (Lewaschew,  Hammerschlag,  v. 
Jaksch,  Legrain),  and  acute  articular  rheumatism  (Weiss).  The 
observations  are  too  small  in  number  to  justify  discussion  of  these 
attempts  at  length. 

Vaccine  and  Variola.  Sternberg  is  to  be  credited  with  having 
demonstrated  the  properties  acquired  by  the  serum  as  a  result  of 
Jennerian  vaccination.  This  author,  whose  investigations  were  con- 
firmed by  Kinyoun,  recognized  that  a  drop  of  vaccine  when  mixed 
with  four  drops  of  serum  of  a  calf  vaccinated  for  two  weeks,  loses, 
at  the  end  of  an  hour  of  contact,  the  power  of  causing  vaccinal  erup- 
tion. 

This  was  the  first  step  in  the  way  of  serumtherapy.  The  authors, 
however,  who  attempted  to  immunize  animals  by  means  of  the  serum 
of  vaccinated  subjects  obtained  results  which  were  not  very  satis- 
factory. We  must  come  to  the  important  work  of  Beclere,  Chambon, 
and  Menard,1  who  demonstrated  that  the  serum  of  a  vaccinated  calf 
when  not  taken  during  the  virulent  period — i.  c,  from  ten  to  fifteen 
days  after  vaccination — possesses,  with  regard  to  the  inoculated  vac- 
cine, immunizing  properties,  provided  very  considerable  amounts  of 

1  Beclere,  Chambon.  and  Menard.  Etudes  sur  l'immuiiite  vaccinale  et  le  pouvoir 
immunisant  du  serum  de  g&risse  vaccinee.    Annates  de  l'Institut  Pasteur,  January,  1896 


734  IXFECTIOUS  DISEASES. 

serum  are  introduced  beneath  the  skin.  It  is  necessary  to  inject  an 
amount  equal  to  one-hundredth  part  of  the  weight  of  the  body,  and 
even  then  the  immunity  obtained  is  incomplete.  A  great  number  of 
inoculations  are  ineffective.  The  eruptions  which  appear  are  rudi- 
mentary. However,  the  most  important  fact  from  a  doctrinal  stand- 
point is  that- the  contents  of  these  eruptions  are  not  virulent.  They 
cannot  be  employed  to  inoculate  other  individuals.  The  authors 
furthermore  remark  that  the  action  of  the  serum  depends  rather 
upon  the  substances  which  are  dissolved  in  it,  since  the  effects  are 
immediate.  Twenty-four  hours  after  the  injection  immunity  is 
effected. 

It  is  evident  that  serumtherapy  cannot  displace  Jennerian  vac- 
cination, and  this  for  two  reasons :  the  amount  of  serum  required  is 
too  great;  the  immunity  produced  is  incomplete  and  is  not  permanent. 
Serumtherapy  may,  therefore,  be  resorted  to  only  in  those  cases  in 
which  non-vaccinated  individuals  are  found  in  contact  with  variolar 
patients,  especially  if  they  present  at  that  moment  some  morbid 
symptoms  announcing  the  invasion  of  variola.  It  would  then  be 
feared  that  vaccine  would  act  too  tardily  to  modify  the  organism  in 
time.  The  serum  is  to  be  utilized  under  such  conditions  and,  if 
necessary,  an  inoculation  with  the  vaccinal  virus  made  at  the  same 
time. 

The  authors,  however,  who  studied  the  vaccinal  serum,  had 
another  end  in  view.  They  looked  for  a  remedy  against  variola.  As 
early  as  1893  Auche,  and  then  Landmann  employed  human  serum 
obtained  from  cured  variola  cases.  They  obtained  no  appreciable 
result.  Landmann  likewise  failed  with  the  serum  of  vaccinated 
heifers,  while  Elliot  saw  a  patient  recover  without  trny  cicatrices 
after  the  injection  of  105  c.cm.  In  another  case,  which  was  a  very 
grave  one,  65  c.cm.  did  not  prevent  the  fatal  termination.  According 
to  Beclere,  the  failures  are  due  to  the  fact  that  the  amount  of  serum 
administered  is  too  small.  This  author  injected  amounts  far  exceed- 
ing those  employed  in  other  diseases.  He  made  use  of  doses  equiv- 
alent to  one-fiftieth  part  of  the  weight  of  the  body  in  adults,  and  to 
the  twentieth  part  in  children.  Thus,  in  a  case  reported  by  him, 
a  woman  weighing  70  kilograms  (155  pounds)  received  1560  c.cm. 
beneath  the  skin  of  the  abdomen  in  one  hour.  This  patient  bore  the 
injection  well  and  rapidly  recovered.  Beclere,  during  the  Marseilles 
epidemic,  treated  ten  cases  of  variola.  Three  of  them  died;  one  of 
them,  however,  had  from  the  beginning  a  hemorrhagic  variola,  the 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8E8.  735 

other  was  a  newborn  suffering  from  athrepsia.  We  may  add  to  the 
list  a  few  cases  treated  by  Dr.  B^clere  in  our  isolation  ward  al  the 
Hospital  of  La  Porte  d'Aubervilliers,    everal  of  them  with 

Owing  to  his  scientific  temper,  Dr.  Be»cl6re  abstain  from  drawing 
any  conclusions  from  his  serumtherapy  method.  The  facts  are  too 
small  in  m mil xt  to  en: 1 1  ilc  one  to  form  a  well  founded  opinion.  There 
is  one  thing,  however,  thai  can  meanwhile  be  affirmed,  viz.,  thai  the 
method  is  harmless.  The  serum,  even  when  administered  in  very 
large  amounts,  is  borne  perfectly.  Hence,  there  is  no  reason  for  not 
continuing  (he  experiments.  Of  course,  the  patients  should  al  the 
same  lime  be  (rented  by  the  usual  means,  and  the  physician  should 
be  glad  to  find  a  useful  auxiliary  in  serumtherapy.  In  view  of  the 
first  results  obtained  and  the  recent  investigations  pursued  by  Dr, 
Courniont,  we  may  conclude  that  the  action  of  the  vaccinal  serum 
should  be  increased  and  rendered  more  energetic.  Although  the 
calves  submitted  to  repeated  inoculations  do  not  seem  to  furnish  a 
more  efficacious  serum,  some  results  may,  perhaps,  be  arrived  al  by 
modifying  the  mode  of  introduction  and  by  injecting,  for  example, 
large  amounts  of  vaccine  into  the  circulatory  system. 

Hydrophobia.  After  the  discovery  of  Richet  and  Hericourt.  Babes 
pursued  a  series  of  studies  on  antirabic  serumtherapy.  Then  fol- 
lowed Tizzoni,  Schwarz,  and  Centanni,  who  added  some  important 
data  to  the  controversy.  In  their  first  experiments  Babes  and  Lepp 
recognized  that  a  dog  after  having  received  for  six  successive  days 
5  c.cm.  of  blood  of  a  vaccinated  dog,  becomes  refractory  to  the  inocu- 
lation of  hydrophobia.  The  result  is  the  same  in  rabbits.  After 
allowing  four  clogs  to  be  bitten  by  hydrophobic  animals,  the  authors 
kept  two  of  them  as  controls.  These  died  within  sixteen  and  twenty- 
eight  hours,  respectively.  The  other  two  received,  for  seven  day.-. 
the  blood  of  the  vaccinated  animals;  one  of  them  died  tardily,  the 
other  resisted.  This  favorable  action  of  the  blood  probably  depends 
upon  a  power  which  may  be  demonstrated  outside  of  the  organism. 
Babes  and  Cerchez,  and  Tizzoni  and  Schwarz  proved  that  when  the 
blood  or  the  serum  of  a  vaccinated  dog  is  left  for  several  hours  in 
contact  with  the  virus  of  hydrophobia,  the  latter  loses  its  pathogenic 
properties.  This  action  seems  to  be  due  to  a  globulin  which  is  soluble 
in  glycerin,  precipitated  by  the  sulphate  of  magnesia  and  by  alcohol, 
ami  does  not  pass  through  the  membrane  of  the  dialyzer  'Tizzoni 
ami  Schwarz).  By  employing  strongly  immunized  animals  we  may 
succeed  in  preparing  a  serum  of  very  great  activity.    From  this  point 


736  IXFECTIOUS  DISEASES. 

of  view,  the  serum  of  Tizzoni  and  Centanni  seems  to  respond  to  all 
requirements.  It  is  prophylactic  in  the  proportion  of  1:25,000  for 
an  inoculation  of  hydrophobic  virus  practised  twenty-four  hours 
later;  in  other  words,  0.04  c.cm.  suffices  to  immunize  a  rabbit  weigh- 
ing 1  kilogram.  The  proportion  falls  to  1  per  cent,  for  the  fixed  virus. 
From  six  to  ten  times  larger  doses  must  be  employed  in  treating 
animals  already  inoculated.  These  doses,  however,  are  not  excessive, 
since,  for  a  man,  they  would  not  exceed  the  amount  of  20  or  25  grams. 

It  would,  therefore,  be  advantageous  to  substitute  serumtherapy 
for  the  Pasteur  method  in  those  cases  in  which  rapid  action  is 
necessary.  Such  is  the  conclusion  reached  by  various  authorities 
who  have  studied  this  question,  notably  that  of  Babes,  who,  since 
1891,  has  employed  this  therapeutic  method  with  success  in  patients 
who  had  been  bitten  by  hydrophobic  wolves. 

Syphilis.  As  all  animals  are  refractory  to  syphilis,  any  species  might 
be  chosen  for  the  first  serumtherapy  attempts.  The  clog,  the  sheep, 
the  lamb,  the  calf,  and  the  rabbit  have  been  made  use  of.  Their 
sera  have  increased  the  strength  of  patients  and  hastened  cicatriza- 
tion of  rebellious  ulcerations.  This  is  practically  the  same  effect  as 
is  at  times  produced  by  the  serum  of  normal  animals  in  tubercular 
ulcerations. 

The  evolution  of  the  disease,  however,  did  not  seem  to  be  in  any 
wise  influenced  by  these  injections.  A  specific  serum  was,  therefore, 
looked  for.  Pellizzari  then  tried  the  method  which  yielded  results 
in  other  diseases.  He  injected  the  serum  obtained  from  syphilitic 
individuals  infected  for  a  greater  or  less  period  of  time.  The  results 
were  insignificant,  a  fact  undoubtedly  due  to  the  too  small  amount 
of  antitoxin  contained  in  the  blood  of  a  syphilitic.  Hence,  it  was 
necessary  to  increase  the  therapeutic  action  of  the  serum.  In  this 
direction  an  attempt  was  made  by  G.  Mazza,  by  injecting  into  ani- 
mals from  10  c.cm.  to  20  c.cm.  of  S}^philitic  blood.  The  author, 
however,  does  not  seem  to  have  pursued  his  researches  with  much 
persistence.  The  question  was  taken  up  by  Drs.  Richet,  Hericourt, 
and  Triboulet,  who  prepared  their  animals — dog  or  ass — with  the 
blood  of  individuals  presenting  roseolar  eruption.  A  few  clays  later 
they  bled  the  animals.  Three  patients  were  submitted  to  the  treat- 
ment. In  this  manner  they  obtained  a  more  or  less  lasting  cica- 
trization of  ulcerations  which  had  resisted  specific  treatment,  and  in 
one  case  they  saw  the  disappearance  of  certain  symptoms  which 
seemed  to  indicate  the  development  of  locomotor  ataxia. 


THEBAPEUTIOS  OF  INFECTIOUS  DISEASES.  7.",7 

At  that  time  Drs.  Gilbert  and  Fournier  published  an  important 
work  in  which    they  described    various  serumtherapy  proced 
Into  a  newly  infected  syphilitic  individual   they  injected  within 
twenty  days  204  ecu],  of  serum  taken  from  an  old  c  ypb- 

ilis.  Under  the  influence  of  this  treatment  the  general  state  im- 
proved, the  aching  of  the  bones  and  head  disappeared,  and  the  erup- 
tions gradually  subsided.  The  results  were  fairly  good,  but  not 
entirely  satisfactory.  Gilbert  and  Foumier  then  resorted  to  goata 
and  dogs,  into  which  they  injected  syphilitic,  blood  in  doses  of  from 
170  to  180  grams,  or  else  they  introduced  beneath  the  skin  of  the 
animals  indurated  chancres,  papuke,  and,  simultaneously,  blood. 
The  so  rum  obtained  from  these  animals  served  to  treat  seventeen 
patients.  In  a  few  cases  the  general  state  was  ameliorated  and  the 
strength  increased,  but  in  several  other  cases  the  method  completely 
failed.  As  the  authors  remarked,  it  is  conceivable  that  there  Bhould 
be  hesitation  of  judgment  in  the  presence  of  such  contradictory  facts. 
From  the  perusal  of  published  observations  it  seems  that  the  serum 
derived  from  normal  as  well  as  from  prepared  animals  may  favorably 
modify  the  general  state  of  the  patients,  stimulate  the  reactions  of 
the  organism,  and  favor  cicatrization  of  atonic  lesions.  These  results 
point  out  the  indications  of  the  method.  In  a  general  manner,  how- 
ever, serumtherapy  is  considerably  inferior  to  the  classical  treat- 
ment. A  similar  conclusion  is  arrived  at  by  Neumann,  who  reported 
a  few  hardly  satisfactory  attempts. 

Prophylactic  Injections  of  Serum.  Prophylaxis  or,  if  the  author  may 
say  so,  vaccination  by  serums,  is  superior  to  vaccination  by  attenu- 
ated microbes  or  soluble  products,  because  it  exerts  an  immediate 
action  and  does  not  cause  the  organism  to  pass  through  a  prepara- 
tory phase  during  which  its  resistance  is  diminished.  On  the  other 
hand,  it  is  inferior,  because  the  immunity  which  it  confers  does  not 
last  long;  it  is  effective  only  for  a  few  days  or  weeks.  It  may.  there- 
fore, be  theoretically  stated  that  it  is  useful  to  vaccinate  individuals 
by  means  of  attenuated  or  sterilized  cultures  in  the  presence  of  an 
epidemic  or  in  view  of  a  future  contamination;  but  we  must  resort 
to  the  serum  in  case  of  urgency,  especially  when  we  fear  that  the 
subject  may  already  have  been  contaminated.  Prophylactic  injec- 
tions of  serum  have  been  employed  in  several  circumstances,  notably 
in  puerperal  women,  in  wounded  individuals,  and  in  those  for  whom 
the  development  of  tetanus  is  feared:  finally  and  particularly,  in 
those  who  have  been  exposed  to  contamination  by  diphtheria.    The 

47 


738  LXEECTIOVS  DISEASES. 

observations  regarding  diphtheria  cases  are  sufficiently  numerous  to 
support  a  conclusion. 

Roux  is  decidedly  in  favor  of  preventive  injections.  Behring  is 
of  the  same  opinion.  He  advises  the  introduction  of  a  small  amount 
of  serum — 1  c.cm.  of  the  Xo.  1 — and  renewal  of  the  injections  every 
six  weeks.  '  Unfortunately,  this  practise  does  not  seem  to  be  suffi- 
cient. The  amount  administered  is  too  small  to  obtain  durable 
immunity.  In  order  not  to  overload  our  work  with  statistics,  we 
shall  be  contented  with  citing  those  given  by  Krasnobaeff.  Out  of 
a  total  of  1965  individuals  preventively  injected,  there  were  43  cases 
of  diphtheria,  three  of  which  died.  Considering  the  results  obtained 
in  children's  hospitals  in  various  countries,  it  is  found  that  out  of 
344  prophylactic  injections  there  were  7  cases  of  diphtheria,  3  of 
which  proved  fatal. 

This  gives  a  death-rate  of  2.03  per  cent.  In  these  same  hospi- 
tals in  non-injected  children  the  mortality  is  about  the  same, 
namely,  2.71  per  hundred. 

It  would  be  an  easy  matter  to  report  a  very  great  number  of  cases 
in  which  prophylactic  injections  have  failed  to  prevent  either  the 
development  of  the  disease  or  a  fatal  termination.  They  do  not, 
therefore,  seem  to  be  very  efficacious.  Their  employment  might, 
nevertheless,  be  recommended  if  the  injections  were  absolutely  harm- 
less. Such  is  not  the  case,  however,  as  we  shall  see  in  the  following 
chapter.  And  it  is  no  wonder,  then,  that  the  prophylactic  method  does 
not  seem  likely  to  become  generally  adopted.  The  author  does  not 
believe  that  physicians,  experimenters,  or  students  connected  with 
diphtheria  wards  receive  from  time  to  time  inoculations  of  the  serum 
as  a  preventive  measure  or  give  such  injections  to  their  families. 
They  are  not  to  blame  if  they  do  not  intervene  before  the  disease  is 
manifested,  because  it  is  not  wise  to  run  the  risk  of  the  various  serum- 
therapy  accidents  with  a  view  of  avoiding  an  eventual  contagion, 
which  is  fortunately  of  very  rare  occurrence.  Although  it  may  be 
resorted  to  under  certain  circumstances,  for  instance,  when  epidemics 
attack  a  college  or  a  ward  of  a  hospital,  or  in  families  in  which  one 
child  has  already  died  and  the  parents  fear  for  the  surviving  children, 
it  does  not  seem  that  the  method  should  be  currently  practised,  for 
there  would  be  no  reason  for  not  regularly  injecting  in  the  near  future 
with  various  prophylactic  serums  with  that  of  typhoid  fever  as  well 
as  of  erysipelas  and  pneumonia.  It  would  be  necessary  to  frequently 
repeat  these  injections,  since  the  immunity  thus  conferred  is  transi- 


THERAPEUTICS  OF  INFECTIOUS  DI8EASE8.  7'.','.) 

lory.    This  would  tend  to  expose  one's  self  to  the  vuriou    accidents 
of  winch  we  are  now  about  to  speak. 

Accidents  Ascribable    to    Serumtherapy.      We  li:i  \  <■  I  hu.    far  reported 

therapeutic  attempts  and  results;  we  have  studied  the  action  of 
serums  regardless  of  the  modifications  and  accidents  which  may  be 
caused  by  their  use.  We  must  now  consider  this  important  question 
which  has  given  rise  to  s  great  Dumber  of  contradictory  contri- 
butions. In  this  connection  we  may  vU'r  to  an  excellenl  resume^ 
namely,  the  thesis  written  by  Dr.  Poix1  upon  our  advice.  I' 
very  complete  monograph,  from  which  we  shall  borrow  a  good  many 
facts. 

Cutaneous  Manifestations.  Abscesses.  Serum  injections  may  pro- 
duce abscesses.  This  is  not,  however,  an  accident  due  to  the  method. 
It  is  at  present  well  demonstrated  that  (he  process  is  one  due  to 
carelessness,  to  insufficient  disinfection  of  the  skin  and  instruments, 
or  to  an  alteration  in  the  serum.  Exception  is  to  be  made  only  with 
regard  to  the  antistreptococcic  serum  obtained  from  animals  immun- 
ized by  means  of  living  cultures.  The  living  microbes  may  then  be 
found  in  the  fluid.  We  have  found  such  to  be  the  case  in  several 
instances  and  recognized  that  the  streptococci  had  preserved  a  cer- 
tain degree  of  virulence.  On  the  other  hand,  numerous  observati ons 
made  upon  man  prove  that  these  injections  may  give  rise  to  ab- 
scesses, phlegmons,  lymphangites,  or  erysipelas,  which  are  at  times 
sufficiently  grave  to  cause  serious  anxiety.  It  is  not  to  be  concluded, 
however,  that  the  antistreptococcic  serum  thus  prepared  is  to  be 
abandoned.  In  order  to  avoid  accidents,  it  suffices  to  take  the  blood 
a  longer  period  of  time  after  the  last  injection  of  the  culture  or  to 
filter  the  serum  through  porcelain.  These  precautions  are  evidently 
quite  elementary,  but  they  must  not  be  overlooked  when  a  product 
is  destined  to  be  used  in  the  treatment  of  patients. 

Exanthemata.  Exanthemata  are  far  more  important.  They  are  not 
like  abscesses,  due  to  defective  preparation;  they  depend  upon  the 
action  of  the  serums  themselves,  and  seem,  therefore,  to  be  unavoid- 
able, as  they  are  caused  by  normal  serum  as  well  as  by  various 
medicinal  serums.  They  generally  make  their  appearance  three  or 
four  days  after  the  injection;  at  times  on  the  tenth  or  even  twentieth 
day.    The  age  of  the  subject  does  not  seem  to  exert  any  influence. 


1  Poix.     Recherches  critiques  et  experimentales  sur  le  scrum  antidiphtenque   (son 
action  sur  l'organisme,  ses  accidents"!.     These  de  Paris,  June.  1S96. 


740  INFECTIOUS  DISEASES. 

and,  what  is  more  difficult  to  explain,  the  accidents  are  in  nowise 
related  to  the  doses  introduced;  1  c.cm.  or  2  c.cm.  may  give  rise  to 
grave  phenomena,  while  10  c.cm.  or  20  c.cm.  of  the  same  sample  may 
be  well  borne.  All  seems  to  depend  upon  individual  predisposition. 
In  certain  cases  the  manifestations  consist  simply  in  the  appearance 
of  various  eruptions,  such  as  urticaria  or  erythema.  In  other 
instances  there  is,  in  addition,  fever  and  arthropathies.  Finally,  in 
certain  rare  instances,  albuminuria,  hemorrhages,  gastrointestinal 
disturbances,  etc.,  appear  after  the  eruption. 

The  frequency  of  serumtherapy  eruptions  varies  greatly  from  one 
time  to  another,  which  is  partly  due  to  the  fact  that  all  horses  do 
not  furnish  identical  serums.  There  are  some  the  sera  of  which  almost 
invariably  cause  eruptions,  while  others  hardly  ever  produce  any. 
It  seems  that  accidents  are  less  frequent  when  the  animals  are  sub- 
mitted to  fasting  before  blood-letting  is  practised.  It  may,  never- 
theless, be  remarked  that  the  eruptions  appear  in  14  per  cent,  of  the 
cases.  This  is  the  figure  given  by  Dubreuilh,  who  reviewed  1946 
observations.  The  same  author  ranges  the  various  eruptions  accord- 
ing to  their  frequency  in  the  following  manner:  urticaria  in  156 
observations;  scarlatiniform  erythema,  46;  polymorphous  erythe- 
mata,  31:  rubeoliform  erythemata,  11.  These  eruptions  generally 
make  their  appearance  from  the  fifth  to  the  thirteenth  day  after  the 
injection.  They  quite  frequently  begin  at  the  point  of  inoculation, 
invade  more  or  less  the  rest  of  the  skin,  but,  in  general,  do  not 
involve  the  face.  Urticaria,  the  most  frequent  eruption,  presents 
nothing  peculiar  in  its  evolution.  It  is  benign  and  transitory.  As 
their  name  indicates,  the  rubeoliform  eruptions  have  the  aspect  of 
measles,  with  which  they  might  be  confounded  if  the  skin  only  was 
examined.  At  times  pure,  they  may  often  be  mixed  with  scarlatini- 
form eruptions.  The  latter  generally  occupy  the  back,  the  flexor 
surfaces  of  the  extremities,  more  rarely  the  thorax,  and  almost  never 
the  face.  They  are  in  many  cases  pruriginous,  whether  urticaria 
coexists  or  not.  As  a  result  of  these  eruptions,  there  is  usually  a 
slightly  marked  desquamation. 

Under  the  name  polymorphous  erythemata  authors  have  some- 
times described  eruptions  characterized  by  mixture  of  several  erup- 
tive types,  sometimes  eruptions  in  which  certain  elements  become 
bullous.  In  some  instances  the  eruption  assumes  a  hemorrhagic 
character  (Mendel)  or  that  of  purpura  (Moizard  and  Perregaux).  The 
cutaneous  manifestations  are  generally  transitory.    They  last  from 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8E8.  711 

three  to  six  days,  but  relapses  occur  in  a  certain  Dumber  ol  c 
They  are  often  attended  by  arthropathie  , 

Arthropathies.  Post-serumtherapy  arthropathies  are  Bimply  char- 
acterized by  particular  pains,  in  most  cai -<•.-■  coincident  ••■  ith eruptions, 
and  never  ending  in  suppuration.  The  only  ob  ervation  of  Buppur- 
ated  arthritis,  that  of  Broca,  is  so  complex  thai  it  cannol  with 
tainty  be  attributed  to  the  serum  injected.  The  articular  gymptonu 
usually  occur  in  the  knee  joint  and  ankle-joint,  and  are  often  attended 
by  muscular  pain  or  neuralgia,  at  times  by  edema  in  the  back  of  the 
hands  and  feet.  These  arthropathies  commonly  disappear  with  the 
eruptions. 

General  state.  Beside  the  eruptions  and  articular  phenomena,  the 
patient  also  presents  a  number  of  general  manifestations.  Fever 
occurs  and  sometimes  reaches  104°  and  even  105.8°  V.  (40°  to 
41°  C).  There1  are  digestive  and  urinary  disturbances.  These  mani- 
festations last  but  a  few  days,  but  the  patient  remains  pale  and  tired. 
In  some  cases,  however,  the  disorders  may  last  for  several  v 
We  must  now  consider  in  a  special  manner  two  scries  of  phenomena 
which  may  occur  separately:  hyperthermia  and  urinary  disorders. 

Fever.  Dr.  Variot  was  the  first  to  call  at  tent  ion  to  the  fever  caused 
by  the  injection  of  serums.  He  proved  its  existence  by  comparing 
a  great  number  of  fever  charts.  We  are  able  to  confirm  his  obser- 
vations on  this  point,  for  patients  who  arrive  at  our  hospital  ward 
devoted  to  adults  are  generally  apyretic.  It  is,  therefore,  very  easy 
to  observe  in  them  the  occurrence  of  hyperthermia  and  to  refer  it 
to  its  true  cause.  The  febrile  movement,  which  is  often  of  a  slight 
and  transitory  character,  may  also  be  observed  when  serum  is 
injected  as  a  prophylactic  into  normal  subjects.  The  temperature 
rises  a  few  tenths  of  a  degree  or  even  two  degrees.  At  the  same  time 
the  pulse  is  accelerated  and  sometimes  becomes  a  little  irregular. 
These  thermal  elevations,  which  occur  a  few  hours,  sometimes  a  day 
or  two,  after  the  injection  of  the  serum,  are  not  to  be  wondered  at. 
The  same  phenomena  occur  in  consequence  of  injections  of  normal 
serum.  This  fact  has  been  observed  in  man  as  well  as  in  animals. 
The  hyperthermizing  action  of  normal  serum  had  been  noted  by 
ourselves,  then  by  Drs.  Mairet  and  Bosc:  but  we  had  practised  intra- 
venous injections.  Poix  made  a  very  careful  comparative  study  by 
injecting  normal  as  well  as  antidiphtheritic  serum  into  rabbits. 
These  injections  were  made  beneath  the  skin,  and  in  both  cases  gave 
rise  to  very  decided  hyperthermia. 


742  ' NFECTIO  US  DISEASES. 

Modifications  of  the  Urine.  Injections  of  serum  seem  to  modify 
in  a  variable  maimer  the  quantity  of  urine  voided.  Some  authors 
have  noted  a  considerable  diminution,  others  an  increase,  still  others 
no  change  at  all.  These  contradictory  results  probably  depend  upon 
the  state  of  the  individual  under  observation.  What  seem  to  be 
more  important  are  the  qualitative  modifications  of  the  urine. 

The  serum  causes  an  increase  in  the  excretion  of  urea  (Mya,  Mon- 
gour,  etc.).  Hyperazoturia  generally  lasts  twenty-four  hours;  then 
the  amount  of  urea  diminishes  and  returns  to  the  normal.  At  the 
same  time  there  is  a  notable  increase  of  phosphates  and  a  slight 
diminution  of  chlorides.  Karlinski,  experimenting  upon  himself, 
found  that  a  subcutaneous  injection  of  10  c.cm.  produced  no  fever 
and  no  urinary  modifications.  This  dose,  however,  is  rather  too 
small  for  an  adult.  By  injecting  larger  amounts  he  noticed  the 
appearance  of  urticaria  and  an  increase  in  urea,  uric  acid,  and  crea- 
tinin.  These  urinary  modifications  lasted  three  days,  but  they  did 
not  depend  upon  the  antitoxin,  since  the  author  observed  analogous 
disorders  with  the  serum  of  a  normal  goat. 

Investigations  pursued  upon  animals  fully  confirm  the  results 
obtained  in  man.  Our  experiments1  and  those  of  Poix  prove  that 
injections  of  serum  produce  slight  polyuria,  an  increase  in  urea  and 
phosphates,  and  a  diminution  in  chlorides.  It  is  to  be  noted,  how- 
ever, that  Poix  has  perfectly  demonstrated  that  these  various 
modifications  are  likewise  produced  under  the  influence  of  normal 
serum. 

All  that  remains  to  say  concerning  the  usual  modifications  of 
the  urinary  secretion  is  that,  according  to  Heckel,  peptonuria  is 
constantly  observed,  and  that,  according  to  Le  Genclre,  urobilinuria 
may  be  observed.  It  now  remains  to  examine  with  particular  atten- 
tion a  more  serious  accident  with  regard  to  which  there  is  no  general 
agreement.    We  refer  to  albuminuria. 

Albuminuria,  Nephritis.  The  most  varied  opinions  have  been 
advanced  concerning  the  disturbances  which  the  serum  engenders 
in  the  kidneys.  As  a  matter  of  fact,  clinical  observations  are  always 
very  complex,  and  it  is  evidently  quite  difficult  to  determine  the 
role  which  is  to  be  respectively  attributed  to  the  principal  infection 
and  to  the  secondary  infections  in  addition  to  those  produced  by 
the  serum.    Some  authors  have,  therefore,  thought,  and  with  good 

1  Charrin  and  Roger.  Action  du  serum  antidiphterique  sur  la  nutrition.  Soc.  med. 
des  hopitaux,  December  14,  1S95. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  743 

reason,  fchat  it  was  necessary  to  study  the  question  by  experimenta- 
tion upon  animals.  Unfortunately,  the  results  obtained  have  been 
quite  contradictory.  Vissman  found  that  the  kidneys  were  con- 
gested, and  he  discovered  by  microscopic  examination  thai  the 
vessels  were  overloaded  with  blood  and  the  cells  of  the  tubuli  filled 
with  refractive  granulations.  The  histological  examinations,  how- 
ever, were  made  upon  fresh  (issues,  because  the  author  believed 
that  reagents  would  prevent  him  from  seeing  the  le  ions.  In  the 
experiments  of  Kossorotoff  the  alterations  were  more  marked. 
There  was  hyperemia,  in  (he  liver  and  kidneys,  and  cloudy  and 
granular  degeneraJ  ion  of  I  he  cells.    The  results  obtained  by  Von 

Kahlden    were  al(oge(her  diflerenl.      A    rahhil    received    16  C.cm.   in 

four  days;  a  guinea-pig  received,  in  the  same  period  of  time,  12  c.cm. 
Microscopic  examination  revealed  no  lesion  in  the  kidneys  and 
myocardium.  Nor  did  Zagari  and  Calabrese  observe  any  renal 
lesions  in  the  animals  which  had  received  serum.  Poix  injected 
into  rabbits  from  5  to  15  c.cm.  of  antidiphtheritic  serum;  two 
animals  received  25  c.cm.  in  three  doses.  Histological  examinai  ion, 
made  by  Dr.  Comte,  revealed  no  appreciable  alteration. 

It  seems,  therefore,  that  the  serum  injected  into  rabbits  and 
guinea-pigs  produces  no  renal  alterations.  This  result  evidently  has 
considerable  value,  but  its  importance  should  not  be  exaggerated. 
It  must  not  be  concluded  that  the  serum  is  incapable  of  producing 
any  alterations  in  man,  since  animals  possess,  in  this  respect,  far 
greater  resistance.  All  experimenters  who  have  attempted  to  create 
nephritis  or  albuminuria  in  animals  know  how  difficult  it  is  to 
succeed  if  brutal  measures  are  not  resorted  to ;  they  also  are  aware 
with  what  facility  the  manifestations  subside  and  disappear.  On 
the  other  hand,  it  should  not  be  overlooked  that  different  animals 
react  differently  against  various  serums.  It  seems,  for  example, 
that  the  rabbit  is  far  more  sensitive  than  man  to  bovine  serum; 
it  may,  however,  be  the  reverse  with  regard  to  horse  serum.  Let 
us  now  see  what  occurs  in  man.  Martin  and  Chaillou  think  that 
the  serum  hinders  the  action  of  the  toxin  upon  the  kidneys  and 
considerably  diminishes  albuminuria.  This  conclusion  may  be 
admitted  with  certain  reservation.  It  is  possible  that  the  serum, 
when  injected  at  the  beginning  of  the  infection,  by  arresting  the 
toxi-infectious  process,  prevents  the  ulterior  alteration  of  the  kidneys ; 
its  action  is  like  that  of  salicylate  of  soda,  which,  by  opposing  the 
evolution  of  acute  articular  rheumatism,  diminishes  the  frequency 


744  INFECTIOUS  DISEASES. 

of  endocarditis.  This,  however,  is  only  a  theoretical  deduction  or 
conception,  since  accurate  information  on  this  subject  is  lacking. 

When  albuminuria  exists  the  serum  does  not  seem  to  ameliorate 
it.  It  is  not  strange  that  such  should  be  the  case.  The  serum  is 
no  more  capable  of  curing  a  renal  lesion  than  salicylate  of  soda  is 
of  curing  rheumatic  endocarditis.  The  anatomical  alteration,  when 
once  established,  continues  its  evolution;  the  serum  is  capable  only 
of  preventing  its  development.  Some  authors,  however,  go  further 
and  accuse  the  serum  of  aggravaitng  pre-existing  lesions,  a  question 
very  difficult  of  solution.  It  is  evidently  necessary  to  resort  to 
experimentation  to  determine  the  result  of  the  injections  of  serum 
into  animals  in  which  renal  alteration  has  previously  been  created. 
This  question  was  investigated  by  Ritter,  who  noticed  that  the 
serum,  when  injected  into  animals  recovering  from  artificial  albumin- 
uria, causes  reappearance  of  albumin  in  the  urine.  On  the  other 
hand,  Zagari  and  Calabrese  injected  serum  into  individuals  suffer- 
ing from  chronic  nephritis,  and  did  not  observe  any  increase  in 
albuminuria.    The  question,  therefore,  requires  more  thorough  study. 

There  remains  a  last  group  of  cases  in  which  the  serum  seems 
surely  to  cause  albuminuria.  Such  is  the  case  when  remote  post- 
serumtherapy  symptoms  supervene.  Several  days  after  the  injection 
of  the  serum,  when  eruptions,  articular  symptoms,  and  febrile 
movement  occur,  albuminuria  also  may  be  observed.  In  this  instance 
it  is  quite  difficult  not  to  attribute  the  urinary  disorder  to  the 
influence  of  the  serum;  for,  in  cases  of  diphtheria  treated  by  the 
usual  procedures,  albuminuria  seldom  makes  its  appearance  so 
tardily.  On  the  other  hand,  the  symptom  forms  part  of  a  whole 
series  of  disturbances  constituting  a  sort  of  clinical  entity;  there  is 
no  reason  for  separating  it  from  the  rest.  In  most  cases,  these 
albuminurias  are  transitory.  In  some  instances,  however,  they 
have  proved  quite  serious.  Elsewhere,  the  renal  disorder  has  been 
expressed  by  anuria,  and  in  other  cases  by  a  hemorrhagic  nephritis. 
The  latter  manifestation  seems  to  us  interesting  because,  in  the 
genesis  of  post-serumtherapy  accidents,  hemorrhages  play  an  im- 
portant role.  Experimenters  had  already  observed  multiple  hemor- 
rhages in  consequence  of  the  introduction  of  foreign  blood  or  serum 
into  animals. 

Hemorrhages.  Besides  hemorrhagic  nephritis  and  cutaneous 
hemorrhages,  notably  purpura,  the  serum  has  sometimes  given  rise 
to  epistaxis  and  uterine  hemorrhages.     D'Astros  made  a  careful 


TllKltAl'KUTKJS  OF  TNFE0TI0U8  DISEASES.  745 

study  of  tin;  action  of  serum  upon  the  uterine  functions,  and  found 
that  when  it  is  applied  at  the  time  of  men  truation  i\  increase  the 
flow;  during  the  interval  it  brings  h  on.  Metrorrhagia  appean  the 
day  following  the  injection,  or  later,  li  generally  coexists  with  ■*' 
cutaneous  eruption.  However,  in  a  case  in  which  the  erum 
injected  into  a  pregnant  woman,  the  progre  o]  pregnancy  wai  in 
nowise  disturbed. 

Modifications  in  the  Blood.  It  is  difficull  i"  Bay  whether  hemor- 
rhages following  serumtherapy  resu.l1  from  an  action  exercised  upon 
the  vasomotors  or  upon  the  blood  itself,  h  is  known  thai  the  serum 
produces  some  interesting  modifications  in  the  constitution  of  the 
blood.  It  diminishes  leucocytosis.  This  is  tiol  a  common  action 
engendered  by  any  serum  whatever.  The  researches  of  Ewing 
clearly  deinonstrated  (hat  il  is  due  to  a  specific  action  of  the  anti- 
toxin. He  proved  it  by  experiments  upon  animals  and  observations 
in  man.  Hypoleucocytosis  lasts  twenty-four  to  forty-eight  hours. 
It  is  especially  the  mononuclears  and,  among  the  polynuclears,  those 
that  are  stained  with  difficulty,  that  disappear.  The  poly  nuclear 
cells  that  are  well  stained  do  not  present  any  modifications.  I'  is 
probably  a  process  of  negative  chemiotaxis,  which  causes  such  an 
accumulation  of  leucocytes  in  the  viscera  that  it  has  been  questioned 
whether  it  is  not  dangerous. 

Another  interesting  phenomenon  is  the  fact  that  the  serum 
increases  the  aptitude  of  the  leucocytes  for  taking  up  dyes.  Toxins 
have  a  reverse  effect.  In  those  cases  in  which  the  injection  of  serum 
does  not  cause  the  reappearance  of  a  normal  tinctorial  reaction  in 
the  leucocytes,  prognosis  may  be  considered  as  fatal.  If  these  facts 
were  confirmed  they  would  constitute  a  very  simple  means  of  fore- 
telling the  evolution  of  diphtheria.  For  the  time  being  we  must  be 
contented  with  the  fact  that  the  number  of  leucocytes  undergoes 
variations.  On  this  point  the  investigations  of  Schlesinger  have 
confirmed  those  of  Ewing:  Out  of  twenty-four  children  suffering 
from  diphtheria,  in  twenty-one  the  injection  of  serum  first  caused 
leucocytosis  to  disappear;  this  was  followed  by  a  slight  secondary 
leucocytosis. 

These  results  are  evidently  interesting  in  view  of  the  important 
role  which  the  leucocytes  plav  in  the  protection  of  the  organism. 
It  is  for  this  reason  that  authors  have  devoted  special  attention  to 
wandering  cells.  It  is  to  be  regretted,  however,  that  they  have 
neglected  the  red  globules.     The  question  was  taken  up  only  by 


746  ISFECTIO  US  DISEASES. 

Zaggari  and  Calabrese,  who  observed  a  diminution  in  the  number  of 

red  corpuscles  and  of  their  richness  in  hemoglobin.  These  researches 
are  particularly  welcome  for  the  reason  that  serum  has  been  held 
responsible  for  some  grave  and  rebellious  anemic  conditions.  Chil- 
dren who  had  received  it  as  a  preventive  are  said  to  have  for  months 
remained  pale,  weak,  and  to  have  presented  furuncular  eruptions, 
which  means  a  marked  disturbance  in  their  nutrition  and  develop- 
ment. This  conclusion  finds  support  in  Dr.  Arloing's  investigations. 
This  author  studied  the  development  of  young  guinea-pigs  into 
which  he  daily  injected  small  amounts  of  normal  or  antidiphtheritic 
serum.  "While  the  controls  increased  34  per  cent,  of  their  initial 
weight,  the  animals  which  received  normal  as  well  as  immunizing 
serum  increased  only  19  or  even  16  per  cent.  The  foreign  serum 
thus  exercises  a  harmful  action,  and  the  longer  the  serum  is  admin- 
istered the  more  marked  is  this  action.  Of  course,  the  quantities 
introduced  were  relatively  more  considerable  than  in  the  case  of 
the  child,  but  we  know  how  resistant  animals  are.  Without  pro- 
ducing such  harmful  results,  they  are  bad  enough  if  only  nutrition 
is  disturbed  and  development  hindered. 

Other  Accidents  Ascribable  to  Serum.  Other  disorders  attribut- 
able to  the  use  of  the  serum  have  been  observed  in  the  course  of  post- 
serumtherapy  syndrome,  coincidently  with  eruptions  and  arthrop- 
athies. These  disturbances  consist  in  vomiting,  profuse  diarrhea, 
sometimes  dysinteriform  and  sanguinolent  diarrhea,  swelling  of  the 
lymphatic  glands  and  spleen,  and,  finally,  cardiac  disorders.  The 
latter  seem  to  be  quite  frequent,  at  least  according  to  observations 
published  in  foreign  countries. 

Baginsky,  who  later  on  changed  his  opinion,  Hunnius,  Schroeder, 
and  Springorum  dwell  upon  cardiac  arythmias,  tachycardia,  and 
bruit  de  galop.  They  likewise  noted  edema  of  the  extremities, 
which  indicates  considerable  weakness  of  the  heart,  and  reported 
observations  in  which  these  various  disturbances  were  quite  serious 
and  alarming.  In  a  case  concerning  a  young  woman  twenty  years 
of  age  we  observed  some  interesting  nervous  manifestations.  In 
taking  care  of  a  three-year-old  child  suffering  from  diphtheria  she 
had  been  bitten  by  the  child  and  received  two  small  abrasions  on 
her  middle  finger.  On  the  following  day,  the  physician  fearing  the 
development  of  cutaneous  diphtheria,  hastened  to  inject  40  c.cm. 
of  serum  into  the  young  woman,  and  sent  her  to  our  hospital.  The 
wounds  presented  a  good  appearance  and  seemed  in  nowise  diph- 


THERAPEUTICS  OF  TNFE0TI0U8  DISEASES.  7  17 

theritic.  For  greater  safety,  however,  culture  were  made,  which 
demonstrated  the  presence  of  no  other  microbes  than  the  staphylo- 
coccus albus.  Eight  days  later  the  symptomi  of  serum  intoxication 
appeared,  with  fever  progressively  attaining  100.4°  and  102.2°  I 
(38°  and  39°  C.)  and  articular  pains.  Two  days  after,  this  woman  had, 
for  the  first  time  in  her  life,  a  well  characterized  attacl  teria. 

From  that  moment  on  a  series  of  neurotic  manife  tatione  appeared. 
First,  convulsive  attacks  which  recurred  for  three  days  in  succe  rion; 
then  the  patient  became  indifferenl  to  everything  aboul  her,  hardly 
replying  to  questions.  The  temperature  oscillated  around  loi  I  . 
(40°  C),  and  pulse  120  per  minute;  the  tongue  was  dry.  A  few 
days  later  she  suffered  from  anuria  for  forty-eighl  hours;  then  she 
had  mutism  for  two  days;  after  that  the  patient  fell  into  an  ecstatic 
state  which  lasted  for  a  week.  A  month  after  the  beginning  of  the 
disturbances  she  recovered. 

It  might  be  supposed  that  in  this  observation  the  question 
one  of  traumatic  hysteria,  excited  by  the  biting.  The  appearanre 
of  nervous  symptoms  forty-eight  hours  after  the  beginning  of  the 
fever  caused  by  the  serum,  however,  seems  to  indicate  that  it  was 
a  case  of  toxic  hysteria  and  that  the  injection  of  the  serum  had 
been  the  cause  of  the  manifestations. 

Prognosis  of  Serumtherapy  Accidents.  We  have  above  described 
the  phenomena  which  may  be  attributed  to  serumtherapy.  These 
unfavorable  symptoms  have  been  observed  mostly  in  consequence 
of  the  use  of  antidiphtheritic  serum.  This  is  due  simply  to  the  fact 
that  this  serum  is  the  only  one  currently  employed,  since  it  seems 
to  be  well  demonstrated  that  the  majority  of  these  phenomena 
are  not  due  to  the  antitoxin,  but  to  an  action  possessed  by  all 
foreign  serums. 

An  injection  of  serum  almost  always  gives  rise  to  a  reaction,  such 
as  transitory  elevation  in  the  temperature,  which,  in  most  cases, 
hardly  deserves  the  name  accident.  This  reaction,  however,  may 
acquire  alarming  intensity  in  certain  subjects  who  are  already  sick. 
This  may  occur  notably  in  tubercular  patients.  Roux  and  Yariot 
agree  that  the  serum  does  not  produce  good  results  in  this  disease : 
it  produces  certain  disturbances,  and  such  is  the  opinion  of  several 
authorities.  The  injection  of  serum  gives  rise  to  a  congestion  just 
like  an  injection  of  tuberculin.  In  several  personal  cases,  one  of 
which  was  reported  in  Poix's  thesis,  we  found  that  the  injection 
of  20  c.cm.  of  serum  caused  a  notable  elevation  in  the  temperature 


748  ISFECTIO  US  DISEASES. 

and  aggravated  the  general  state  of  the  patient.  In  the  case  pub- 
lished by  Poix  the  patient  died  seven  days  later,  and  the  necropsy 
revealed  advanced  tubercular  lesions.  It  is  difficult  to  say  what 
the  respective  role  of  tuberculosis,  of  diphtheria,  and  of  the  serum 
had  been  in  this  fatal  termination.  "We  believe,  however,  that  in 
cases  of  tuberculosis,  at  least  of  adults  whose  lesions  are  well  pro- 
nounced, it  is  necessary,  if  diphtheria  is  not  too  grave,  to  abstain 
from  injecting  serum  and  have  recourse  to  simple  local  treatment. 

Barring  this  particular  case,  truly  serious  accidents  are  those 
which  constitute  the  tardy  syndrome.  While  in  most  cases  the 
phenomena  are  transitory  and  in  nowise  disquieting,  they  at  times 
last  for  four  and  five  weeks.  In  other  instances  terrible  manifesta- 
tions, such  as  anuria  and  collapse,  have  been  observed  (Thibierge). 
It  is  true,  however,  that  except  in  a  few  cases  the  patients  have 
generally  recovered. 

"We  here  arrive  at  a  much  disputed  problem.  May  death  result 
from  serumtherapy?  We  may  recall  the  communication  of  Moizard 
and  H.  Bouchard1  and  the  bitter  discussion  to  which  it  gave  rise. 
Guinon  and  Rouffilange2  published  an  analogous  case,  and  others 
may  easily  be  found  in  foreign  literature.  It  is  true  that  several 
of  these  cases  cannot  bear  criticism;  such  is  notably  the  strange 
observation  of  Langerhans'  boy.  There  are  others,  however,  which 
cannot  be  easily  explained  away.  One  such  interesting  case  is  that 
related  by  Izor  Alfolcli:  Forty-eight  hours  after  an  injection  of 
2  c.cm.  of  Behring's  serum  No.  1,  administered  as  prophylactic, 
a  three-year-old  child  developed  fever.  The  temperature  rose  to 
104°  F.  (40°  C.)  attended  by  lumbar  pains  and  much  albuminuria. 
On  the  third  clay  the  child  had  nausea,  an  eruption  of  petechia  on 
the  body,  and  died  the  fourth  day.  The  mechanism  of  these  pheno- 
mena is  open  to  discussion,  but  it  is  hardly  possible  not  to  admit 
a  relation  of  cause  and  effect  in  the  fact  of  so  typical  a  syndrome 
appearing  a  few  days  after  an  injection  of  the  serum  in  a  child 
which  until  then  was  perfectly  healthy.  It  seems  to  me  that  nothing 
is  gained  by  systematically  explaining  away  such  observations  or 
interpreting   them   in  such  a  manner  as   to  clear  serumtherapy  of 

1  Moizard  and  Bouchard.  Un  cas  d'angine  non-diphterique,  traits  par  le  serum,  suivi 
de  mort.     Societ6  medicale  des  hopitaux,  July  5,  1895. 

2  Guinon  and  Rouffilange.  Un  cas  d'angine  membraneuse  traite  par  le  serum  de 
Roux;  mort  avec  anurie  et  convulsions  uremiques.  Revue  mens,  des  maladies  de 
l'enfance,  March,  1895. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  7l!> 

all  responsibility,  [t  Is  better  bo  acknowledge  frankly  thai  erum 
may  produce  some  accidents.  At  all  events,  whal  medicine  i 
be  considered  perfectly  harmless?  Is  there  any  active  ufa  tance, 
even  chemically  well  defined,  which  never  occa  ion  any  disturb- 
ances? Only  those  who  endeavor  forcibly  to  tran  fer  mathematical 
data  into  the  domain  of  biology  can  imagine  thai  il  i-  po  rible  to 
fix  immutable  doses  and  establish  a  formula  in  which  dang< 
and  fatal  doses  will  be  precisely  indicated.  In  reality,  facte  are 
more  complex.  The  experimenter  himself  musl  take  into  account 
the  individual  peculiarities  of  animals.  As  regards  serum  particu- 
larly, individuals  of  the  same  race,  age,  and  weigh!  read  very 
differently  against  the  same  fluid.  The  investigations  of  Bayem, 
Mairet,  Bosc,  and  of  ourselves,  demonstrated  this  fact  beyond  all 
dispute.  The  same  is  undoubtedly  (rue  of  man,  whose  idiosyncrasies 
are  far  more  marked.  In  proportion  as  the  nervous  functions  are 
more  perfected  and  complicated  the  results  become  less  and  less 
fixed,  while  sensitiveness  to  toxic  agents  becomes  more  and  more 
pronounced.1 

We  should  say  that  the  disturbances,  at  any  rate  exceptional, 
which  may  occur  in  consequence  of  serum  injections,  must  by  no 
means  restrict  the  employment  of  the  method,  but  impel  experi- 
menters and  clinicians  to  perfect  it.  Since  most  of  the  dangerous 
phenomena  are  due  to  the  serums,  and  are  independent  of  the 
antitoxin,  the  efforts  of  experimenters  should  be  directed  to  the 
preparation  and  isolation  of  the  active  substance.  The  day  when 
we  possess  a  product  which,  if  not  pure,  is  at  least  freed  from  a 
great  number  of  useless  or  harmful  substances,  decided  progress 
will  have  been  accomplished.  Meanwhile,  we  are  fortunate  to 
possess  a  therapeutic  method  which  has  notably  reduced  the  death- 
rate. 

Causes  and  Mechanism  of  the  Accidents.  It  is  impossible  to 
argue  to-day  that  the  disturbances  following  serumtherapy  are  due 
to  diphtheria  itself,  or  that  they  are  produced  only  after  such  grave 
cases  of  diphtheria  which,  without  the  new  treatment,  would  termi- 
nate in  death.  The  appearance  of  similar  manifestations  in  healthy 
subjects  who  have  received  preventive  injections,  or  in  persons 
suffering  from  non-diphtheritic  anginas,  suffices  to  invalidate  this 

1  There  will  be  found  a  number  of  facts  demonstrating  individual  sensibility  to  toxic 
agent  in  the  author's  article.  '•  Intoxications."  Traite  de  pathologie  generate,  Paris,  1S95, 
vol.  i.  p.  S49. 


750  INFECTIOUS  DISEASES. 

explanation.  On  the  other  hand,  identical  disturbances,  not  only 
eruptions,  but  articular  symptoms,  fever,  gastric  disorders,  and 
hemorrhages  occur  in  consequence  of  injections  of  normal  serums. 
It  is  not,  therefore,  the  antitoxin  that  is  responsible  for  the  disorders 
but  the  introduction  of  a  foreign  serum. 

It  cannot- be  objected  that  nothing  of  the  kind  occurs  when  the 
blood  of  horses  is  injected  into  rabbits,  for  it  is  possible,  with  other 
serums,  to  obtain  results  comparable  to  those  occurring  in  man. 
If  the  blood  of  dogs  is  introduced  into  rabbits,  albuminuria  and 
hemorrhages  often  appear.  The  results  are  still  more  interesting 
when  cow's  serum  is  injected  into  dogs.  According  to  Dr.  Hayem, 
considerable  individual  differences,  resistances  altogether  dissimilar 
from  one  individual  to  another,  are  observed.  The  same  injection 
may  produce  nothing  in  one  dog  and  cause  in  another,  apparently 
identical  with  the  first,  hemorrhages,  anuria,  or  albuminuria,  and 
even  death.  This  is,  therefore,  as  far  as  is  possible  in  experimentation, 
the  reproduction  of  what  occurs  in  clinical  experience. 

These  facts  will  serve  to  refute  a  very  ingenious  theory  advanced 
by  Sevestre.1  This  able  clinician  divides  serumtherapy  disturbances 
into  three  groups:  Those  immediately  following  the  injection  of 
the  serum,  viz.,  elevation  in  the  temperature  and  acceleration 
of  the  pulse — accidents  which,  like  the  preceding  ones,  are  due  to 
the  serum.  Such  is  flying  urticaria,  appearing  from  the  fourth  to 
the  sixth  day.  Finally,  the  tardy  disturbances,  namely,  those  of 
a  serious  character,  including  various  exanthemata,  albuminuria  and 
articular  disorders.  Regarding  these  Sevestre  does  not  admit 
that  they  are  due  to  the  action  of  the  serum,  but  he  attributes 
them  to  the  influence  of  streptococci,  viz.,  to  secondary  infections. 
His  theory  has  not  manj^  adherents.  It  seems  to  me  hardly 
acceptable,  for,  as  it  has  already  been  stated,  the  serum  causes  the 
same  disturbances  in  individuals  suffering  from  chronic  infections, 
and  in  normal  subjects.  All  that  may  be  admitted  is  that  by  dis- 
turbing the  organism  the  serum  may  favor  the  development  of 
microbes  until  then  inoffensive.  It  may  also  be  admitted  that 
certain  symptoms  are  of  an  infectious  order.  For  instance,  dysenteri- 
form  diarrheas  may  be  due  to  exaltation  of  intestinal  bacteria. 
Analogous  symptoms  are  observed  in  the  course  of  a  great  number 
of  intoxications.     A  well-known  instance  is  mercurial  stomatitis  or 

1  Sevestre.  Des  accidents  imputables  a  la  s'rumtherapie  ou  au  streptocoque  dans 
la  diphterie.     Soc.  med.  des  hopitaux,  July  19,  1S95. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  7r,\ 

enteritis.    The  microbes  of  the  mouth  and  of  the  inte  tine  c 
these  lesions,  but  their  action   is  rendered   possible  through   the 
intervention  of  mercury.     Mercurial  stomatiti    and  enteritis  musl 
remain  among  toxic  affections,  and  the  same  i    true  of  po  I    'ruin 
therapy  accidents. 

Among  the  substances  contained  in  the  serum,  i1  is  the  albumins 
that  are  probably  the  active  agents.  The  numerous  experimental 
investigations  which  have  shown  the  dangers  of  heterogenous  trans- 
fusions have  demonstrated  thai  all  the  disturbances  depend  upon 
albuminoid  matters.  On  the  other  hand,  the  research©  of  Mairel 
and  Bosc proved  that  heating  the  serum  between  132.8°  and  L38.2  I  . 
(56°  and  59°  C.)  may  abolish  its  coagulating  and  globulicidal  prop- 
erties, but  its  toxic  action  remains  intact.  Therefore,  the  blood 
docs  not  produce  disturbances  by  destroying  the  globules  of  the 
transfused  individual  or  by  causing  coagulation  in  the  vessels. 

For  the  time  being  we  are  unable  to  further  elucidate  I  he  mechan- 
ism of  the  phenomena.  We  do  not  know  whether  the  direct  action 
of  the  foreign  albumin  or  that  of  the  products  resulting  from  its 
decomposition  are  responsible,  or  whether  we  must  admit  the 
secondary  formation  of  noxious  products  within  the  organism. 

Mode  of  Action  of  Therapeutic  Serums.  After  all  the  develop- 
ments above  presented  regarding  the  chemical  modifications  occur- 
ring in  vaccinated  animals  and  concerning  the  special  characters  of 
their  serums,  the  mode  of  action  of  the  latter  will  be  briefly  con- 
sidered. 

Two  principal  theories  have  been  advanced:  One  of  them 
endeavors  to  reconcile  the  results  of  serumtherapy  with  the  ex- 
clusively phagocytic  doctrine;  the  other  seeks  for  a  purely  humoral 
explanation.  In  the  first  place,  it  is  supposed  that  therapeutic 
serums  act  by  stimulating  the  activity  of  the  wandering  cells  and 
by  increasing  their  phagocytic  power.  If.  in  certain  instances,  the 
serum  acts  more  energetically  when  injected  into  the  adjacent  parts 
of  a  local  lesion,  this  is  due  to  the  fact  that  it  exercises  a  positive 
chemotaetic  action;  it  calls  out,  so  to  say.  and  attracts  the  leuco- 
cytes to  the  point  threatened.  The  active  substance  would  then 
deserve  the  name  stimuli n. 

Several  objections  could  be  raised  against  this  hypothesis.  By 
means  of  very  ingenious  experiments,  Denys  and  Leclef  demon- 
strated that,  in  rabbits  vaccinated  against  the  streptococcus,  the 
leucocytes  are  not  more  active  and  aggressive  than  in  normal  rabbits. 


752  INFECTIOUS  DISEASES. 

Whether  or  not  the  animals  are  refractor)-,  the  leucocytes  do  not 
attack  the  virulent  microbes;  they  seize  only  those  which  have  been 
altered  by  the  curative  serum.  These  researches  bring  us  to  the 
theory  which  we  have  always  advocated,  viz.,  that  immunity  is  the 
result  of  the  co-operation  of  two  principal  factors:  the  plasma  or  the 
scrum,  which  temporarily  weakens  the  microbe,  and  the  leucocyte, 
which  picks  up  and  destroys  it.  Were  it  not  for  the  previous  action 
of  the  fluids  the  phagocytes  would  be  powerless  and  the  infection 
would  develop,  and  without  the  terminal  action  of  the  phagocytes 
the  microbes,  which  were  temporarily  weakened,  would  finally  prove 
victorious,  as  they  do  in  vitro  ;  the  infection  would  be  delayed  but 
not  arrested. 

Let  us  apply  these  data  to  serumtherapy.  By  injecting  the 
prophylactic  or  curative  serum,  we  assist  an  organism  which  secretes 
antibacterial  or  antitoxic  substances ;  since  from  the  very  beginning 
of  the  infection,  or  at  least  in  some  cases,  the  organism  reacts  against 
the  microbe  and  endeavors  to  oppose  it  by  substances  which  hinder 
its  development.  This  protective  secretion  may  be  insufficient  or 
tardy.  We  then  come  to  the  assistance  of  the  struggling  economy 
by  furnishing  it  with  substances  formed  in  another  organism.  If 
the  animal  furnishing  the  blood  is  endowed  with  an  immunity  just 
sufficient  for  itself,  its  fluids  will  prove  to  be  of  moderate  activity 
and  the  result  will  be  almost  negative.  If,  on  the  contrary,  the 
animal  is  hypervaccinated,  its  fluids  will  contain  an  excess  of  pro- 
tective substances,  and  the  small  amount  injected  will  contain  a 
sufficient  quantity  of  antibacterial  or  antitoxic  matters  to  favorably 
modify  the  morbid  evolution. 

Serumtherapy  is,  therefore,  nothing  else  than  a  variety  of  anti- 
septic or  antidotal  medication.  In  the  case  of  an  antibacterial 
serum,  serumtherapy  introduces  into  the  organism  a  specific  anti- 
septic which  hinders  the  vegetation  and  activity  of  the  microbe. 
When  the  serum  is  antitoxic  it  introduces  a  substance  which  affects 
the  cells  of  the  patient,  increases  their  resistance  or  prevents  their 
impregnation.  While  the  theory  of  stimulins  may  be  comprehended 
when  we  consider  the  struggle  against  living  bacteria,  it  is  no  longer 
intelligible  when  we  consider  the  antitoxic  role  of  serums.  In  fact, 
the  experiments  of  Chatenay  and  Metchnikoff  demonstrate  that  the 
number  of  the  leucocytes  diminishes  when  the  animal  succumbs  to 
an  intoxication,  and  that  it  increases  if  the  animal  is  vaccinated  and 
rendered  resistant.    Must  it  be  concluded  that,  in  the  latter  instance, 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  ::,.; 

the  leucocytes  pick  up  the  toxic  ubstance  ,  and  must  we  thus 
extend  to  all  the  poisons  the  theory  which  ome  authoi  endi 
to  establish  concerning  peptone?  Such  conclu  ion  eem  to  be 
premature.  To  deduce  such  an  importanl  action  from  the  imple 
fact  that  the  leucocytes  increase  in  number  when  a  toxic  ubstance 
is  injected  into  a  refractory  animal  seems  to  u  to  make  too  much 
of  such  a  result.  Before  admitting  or  rejecting  the  hypothe  i 
must  demand  experimental  facts,  and  especially  a  careful  demon- 
stration of  the  r61e  played  by  the  antitoxic  function*  of  organs  in 
vaccinated  animals.  Serums  have  such  an  importanl  pecific  action 
that  no  one  has  given  any  attention  to  the  other  effects  which  they 
may  produce  in  the  organism.  In  order  to  completely  appreciate 
their  mode  of  action  and  explain  certain  cases  in  which  a  serum 
has  acted  against  an  infection  of  another  nature,  it  must  be  re- 
membered that  the  normal  serum  or  even  saline  solutions  may  very 
favorably  modify  the  course  of  various  infectious  or  non-infectious 
diseases.  We  have  already  stated  that  the  serum  of  certain  animals 
is  capable  of  favoring  cicatrization  of  the  most  varied  ulcerated 
lesions,  notably  syphilitic  and  tubercular  lesions.  Reinach  tried  in 
cholera  infantum  the  serum  of  cows  or  horses,  of  which  he  injected 
from  10  to  20  c.cm.  Out  of  twenty-five  children  thus  treated  only 
four  died,  and  these  suffered  from  pneumonia.  In  consequence 
of  the  injection,  the  pulse  improved,  cyanosis  disappeared,  and  the 
extremities  became  warm.  These  good  results  are  probably  due. 
at  least  in  part,  to  the  nutritive  value  of  the  serum.  According  to 
this  author,  20  c.cm.  of  serum  correspond  to  150  grams  of  mother's 
milk.  It  may  be  asked,  however,  whether  the  serum  of  animals, 
like  saline  solutions,  does  not  exert  an  indirect  action  upon  infections 
by  modifying  the  state  of  the  nervous  system.  The  results  obtained 
in  the  treatment  of  neurasthenia  and  the  modifications  produced 
in  the  arterial  tension  give  a  certain  value  to  this  hypothesis.  These 
secondary  influences  may,  of  course,  be  ignored  when  we  consider 
the  action  of  specific  serums.  They  are  interesting  only  when  we 
look  for  an  explanation  of  the  favorable  effects  obtained  with  such 
serums  as  are  of  moderate  activity  or  which  are  obtained  from 
normal  animals. 

Conclusions.  In  spite  of  the  numerous  investigations  to  which 
serumtherapy  has  given  rise,  we  must  acknowledge  that  it  has  not 
given  undeniable  practical  results  except  in  diphtheria.  Even  in 
this  instance  its  efficacy  is  not  so  great  in  man  as  would  be  expected 

48 


75-1  INFECTIOUS  DISEASES. 

from  experiments  pursued  upon  animals.  The  same  remark  is  appli- 
cable with  more  force  to  other  serums,  all  of  which  are  capable  of 
saving  laboratory  animals  experimented  upon  and  so  often  fail  when 
tried  on  patients.  This  divergence  between  clinical  and  experimental 
results  may  readily  be  explained.  The  animals  upon  which  experi- 
ments are  pursued  have  been  made  ill  by  artificial  means.  Conse- 
quently, they  were  in  a  state  of  perfect  health  and  in  nowise  disposed 
to  be  invaded  by  the  infection.  It  was  necessary  to  overcome  their 
resistance  brutally,  and  this  unexpected  arrival  of  microbes  aroused 
immediately  a  prompt  and  vigorous  reaction  on  the  part  of  the 
organism  invaded.  On  the  other  hand,  the  artificial  disease  is  simpler, 
since  it  remains  for  a  long  time  monomicrobic.  Lastly,  the  treatment 
is  applied  in  due  time.  A  few  hours,  one  day  at  the  latest,  after  the 
inoculation  intervention  takes  place  in  the  first  stage  or  even  during 
the  stage  of  incubation,  while  no  morbid  symptom  has  as  yet  ex- 
pressed or  revealed  the  invasion  of  the  organism.  In  the  case  of 
man,  however,  the  situation  is  altogether  different.  Except  in  rare 
instances,  infection  is  not  inoculated.  Even  in  cases  of  traumatism 
the  microbes  are  introduced  in  too  small  numbers  to  admit  compari- 
son with  what  occurs  in  the  laboratory.  If,  therefore,  disease  is 
produced,  it  is  due  to  a  morbid  predisposition,  a  previously  debili- 
tated state  of  the  organism;  its  resistance  was  not  artificially  over- 
come in  a  brutal  manner,  but  was  progressively  reduced  by  a  series 
of  preparatory  conditions.  Hence,  when  the  microbe  penetrates, 
reaction  does  not  occur  immediately,  and  is  often  incomplete  or 
insufficient.  On  the  other  hand,  the  disorders  which  have  prepared 
the  development  of  the  infection  or  the  previous  diseases,  of  which 
no  apparent  traces  are  presented  by  the  subject  at  the  moment  of 
the  attack,  may  have  produced  more  or  less  profound  visceral  lesions 
which  added  their  unfavorable  influence  to  that  of  the  infectious 
agents.  Finally,  the  natural  disease  is  not  so  simple  as  the  artificial, 
for  it  is  seldom  monomicrobic.  Several  bacteria  are  almost  always 
called  into  play,  and  thus  modify  the  clinical  course  and  increase  the 
complexity  of  each  case. 

Hence,  when  we  intervene  by  the  serumtherapy  method  we  face 
a  disease  dependent  upon  a  series  of  various  causes  and  the  evolution 
of  which  is  advanced,  for  a  whole  period  of  incubation  and  of  pro- 
dromes has  elapsed  during  which  there  has  been  no  clear  diagnosis 
of  the  nature  of  the  infection.  When  the  symptoms  are  clear  and 
the  diagnosis  is  established  it  may  be  too  late  to  intervene.    Such 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

is  fche  case  in  tetanus.  It  there  ii  yet  time,  the  physician  hesitate* 
to  apply  aew  methods,  and  thus  there  i  a  delay  which  sometimes 
renders  intervention  useless.  Let  us  uppose  thai  action  hat  been 
taken  indue  time,  from  the  beginning  of  the  disorders,  are  wr< 
of  obtaining  favorable  results?  Evidently  not.  The  serum  may 
combat  bacterial  intoxication,  it  may  oppose  the  development  of  the 
microbes,  it  may  neutralize  their  products  of  secretion,  bul  it  can 
accomplish  nothing  against  concomitanl  autointoxications.  The 
organs  altered  by  previous  diseases  or  by  the  present  malady  can 
no  longer  fulfil  their  functions  in  transforming  or  eliminating  the 
toxins  of  cellular  origin.  ( )n  I  he  ol  her  hand,  it  is  to  be  remembered 
that  there  is  an  exaggerated  production  of  poisons  resulting  from 
the  nutritional  disorders  engendered  by  the  disease.  In  view  of 
these  facts  it  is  impossible,  even  when  infection  is  monomicrobic,  to 
draw  conclusions  from  animal  to  man.  Hence,  serums  succeed  better 
in  laboratories  than  in  clinical  experience,  and,  for  this  reason,  old 
therapeutic  methods  should  not  be  abandoned. 

Under  the  influence  of  the  enthusiasm  which  was  aroused  by  anti- 
diphtheritic  serumtherapy,  many  believed  that  traditional  thera- 
peutics had  served  its  time.  Many  believed  thej^  perceived  the  dawn 
of  a  new  era  when  medicine  would  be  simplified  in  a  marvellous 
manner:  no  more  auscultation,  no  more  examination  of  patients;  it 
would  suffice  to  look  for  the  pathogenic  microbe  and  immediately 
inject  the  corresponding  serum.  These  ideas,  which  were  sustained 
by  some  eminent  scientists,  do  not  conform  to  the  reality.  To  thus 
exaggerate  the  value  of  even  such  a  magnificent  method  tends  to 
bring  it  into  discredit  and  to  expose  one's  self  to  cruel  disappoint- 
ments. This  medication  of  equation,  to  use  an  expression  of  Lan- 
douzy,  will  not  succeed  in  therapeutics  any  more  than  elsewhere. 
Biological  phenomena,  especially  pathological  manifestations,  are  too 
complex  to  be  modified  by  simple  and  uniform  procedures.  Serum- 
therapy  is  not  destined  to  do  away  with  the  other  methods.  It  must 
simply  be  considered  as  a  new  means  to  be  employed  concurrently 
with  others.  In  the  case,  for  instance,  of  a  woman  suffering  from 
puerperal  fever,  whatever  may  be  our  confidence  in  serumtherapy, 
we  should  never  resort  to  an  exclusive  method.  We  must  continue  to 
practise  curettage,  intra-uterine  irrigations,  and  prescribe  cold  baths, 
being  convinced  that  it  is  necessary  to  employ  multiple  measures  of 
various  effects  in  order  to  combat  multiple  phenomena  of  various 
origins. 


756  INFECTIOUS  DISEASES. 

AVhile  we  cannot  say  too  much  in  approval  of  the  efforts  of  those 
pursuing  researches  upon  specific  serums,  we  must,  in  the  interest  of 
clinical  experience,  protest  against  the  exclusive  employment  of 
laboratory  methods.  We  have  endeavored  to  show  why  a  sick  man 
is  not  comparable  to  an  inoculated  animal.  It  is  not  sufficient  to 
combat  the  microbe,  since,  in  this  manner,  post-infectious  lesions 
would  be  left  free  to  follow  their  evolution  and  the  patient  would 
succumb  to  autointoxication. 

Although  it  is  not  safe  to  forecast  the  future,  the  author  does  not 
believe  that  serumtherapy  is  destined  to  revolutionize,  completely 
the  art  of  healing.  The  method  has  supplied  a  new  means  of  defense 
and  success;  it  has  enabled  clinicians  to  reduce  the  death-rate  and 
triumph  where  they  formerly  failed.  The  results  are  already  suffi- 
ciently marvellous ;  there  is  no  need  of  exaggerating  them  or  of  dis- 
crediting other  methods.  By  the  whole  of  reasoned  procedures  it  is 
possible  to  overcome  complex  symptoms.  The  indications  of  serum- 
therapy  should  be  determined,  and  it  should  be  associated  with 
other  methods.  Such  is  the  path  which  clinicians  should  follow.  In 
the  meantime  experimenters  will  perfect  the  methods.  They  will 
succeed  in  purifying  the  antitoxins  and  freeing  them  from  useless  or 
harmful  substances  accompanying  them.  This  is  the  imminent  dis- 
covery. When  it  is  achieved,  a  new  advance  will  have  been  made 
in  serumtherapy,  a  new  result  acquired  for  the  consolation  of 
humanity. 


CM  A  PT  E  R     XXIII. 
THERAPEUTICS  OF  [NFECTIOUS  DISEASES  {Concluded). 

Physiological  Medication,     Method     De  Lgned  to  In  <"<■  <!"■  Function  of  I 
Protective  R61e  <>f  the  Liver.    Importance  of  AJimenl    and  ->f  Cold  Enem 
oation  by   Ether.     Protective   Rdle  of  the   Lung;  Rdle  of  the  Blood.     Oxidizing 
Method.    Rdle  of  the  Emunctories.    Sialogogues;  Diuretic  ;Expectoran1    ;Emei 

Purgatives.    Treatment  of  [nfli atorj    Manifi    tation       Local  Treatment.     II"- 

Applications.  Refrigeration,  [mmobilization  and  Compre  ion.  Depletion.  Re- 
vulsion. Indications  and  Mechanism  ol  Revul  Lon.  Vasomotor  Medication 
Treatment  of  Serous,  Purulent,  and  L'seudomembranou  Exudates,  oi  Qangrenoui 
and  Nodular  Lesions.  Treatmenl  of  Hemorrhages.  Chloride  of  Calcium.  \ 
constrictors.  Astringents.  Gelatin.  Treatmenl  of  Fever.  <  <>1.1  and  Hoi  Ba 
Brand's  Method.  Balneotherapy  Rules  for  Typhoid  Fever,  Scarlatina,  Variola, 
Pneumonia,  Bronchopneumonias,  and  Erysipelas.  Chemical  Antithermal  Med- 
icines. Blood-letting;  Mode  of  Action  and  Indications.  Injections  of  Artificial 
Serum:  Their  Action  on  Absorption,  on  Renal  Elimination,  on  the  Nervous  System, 
and  on  Nutrition.  Indications  for  Subcutaneous  and  Intravenous  Injections  of 
Artificial  Serum.  Symptomatic  Medication.  Treatment  of  Nervous,  Cardiac,  and 
Vascular  Disturbances  and  Disorders  of  the  Respiratory,  Alimentary,  and  the 
Urinary  Apparatus. 

Physiological   Medication. 

All  the  forms  of  medication  we  have  thus  far  studied  were  directed 
against  the  pathogenic  agent.  Their  object  was  to  destroy  the  invad- 
ing microbes,  hinder  their  development,  and  neutralize  their  toxins. 
The  antiseptic  and  antitoxic  medications  represent  the  two  principal 
methods  which  resume  the  endeavors  made  in  this  direction.  Serum- 
therapy  particularly  belongs  to  this  group.  It  possesses  a  special 
interest,  because  it  constitutes  a  naturalistic  method.  By  introduc- 
ing a  specific  serum  we  accomplish  sooner  what  the  organism  would 
later.  Investigations  in  pathological  physiology  teach  us  that  during 
infections  certain  organs  endeavor  to  destroy  microbes  and  neutralize 
or  eject  poisons.  Therefore,  in  the  stud}'  of  the  reactions  of  the 
organism  we  may  find  important  therapeutic  indications. 

The  efforts  of  the  physician  must  tend  to  assure  the  function  of 
the  protective  organs  or  promote  their  action.  In  all  probability 
most  of  the  cells  of  the  organism  play  a  role  in  its  protection.  As 
yet  we  are  acquainted  with  but  a  small  side  of  the  question.  We 
know  that  the  liver  is  capable  of  arresting  and  destroying  certain 


758  IXFECTIOUS  DISEASES. 

microbes  and  toxins,  and  that  the  lungs  act  in  the  same  way.  We 
know  that  poisons  may  be  eliminated  through  secretions,  and  par- 
ticularly through  the  renal  secretions  and  accessorily  by  the  secre- 
tions of  the  digestive  canal.  Finally,  we  know  that  the  fight  against 
microbes  and  then  toxins  in  the  interior  of  the  organism  is  assured 
by  chemical  modifications  occurring  in  the  plasma  and  by  the  par- 
ticipation of  a  great  number  of  wandering  cells.  These  changes  in  the 
fluids  and  cells  are  dependent  upon  increased  activity  of  the  hema- 
topoietic organs — of  the  spleen,  lymphatic  glands,  bone-marrow,  and, 
in  young  children,  the  thymus  gland. 

In  spite  of  numerous  studies  pursued  on  this  subject,  the  facts 
are  as  yet  imperfectly  known.  Nevertheless,  certain  among  them 
may  already  be  taken  as  a  starting  point  for  some  therapeutic  indi- 
cations. 

Protective  Role  of  the  Liver.  Among  the  organs  playing  an 
important  role  in  the  protection  of  the  organism  against  infections 
the  liver  deserves  to  be  placed  at  the  head  of  the  list.  Some  years 
ago  we  demonstrated  that  this  organ  was  capable  of  arresting  and 
neutralizing  a  variety  of  poisons  of  external  origin  or  formed  within 
the  diseased  organism.  More  recent  experiments  enabled  us  to 
affirm  that  this  protective  action  extends  to  toxins,  at  least  to  some 
of  them,  and  to  some  microbes.  Whether,  however,  the  question  is 
one  of  soluble  products  or  of  figurate  elements,  the  action  of  the  liver 
is  not  exercised  unless  the  parenchyma  contains  glycogen.  No  mat- 
ter whether  this  substance  plays  an  active  role  in  the  phenomena  of 
defense,  or  whether  it  represents  simply  an  evidence  of  cellular  activ- 
ity, the  only  interesting  point  is  that,  to  a  certain  extent,  it  enables  us 
to  measure  the  activity  of  the  liver  and  determine  with  accuracy  the 
function  of  the  gland.  Knowing  the  conditions  under  which  glycogen 
is  diminished  or  increased,  we  are  able  to  lay  down  therapeutic  indi- 
cations calculated  to  maintain  the  protective  activity  of  the  liver. 

It  is  often  repeated  that,  for  this  purpose,  it  is  indispensable  to 
combat  hypothermia.  Fever  is  said  to  cause  the  disappearance  of 
glycogen.  This  statement  is  exaggerated.  When  hyperthermia  is 
engendered  by  inoculation  of  an  infectious  microbe  glycogen  remains 
intact  during  the  febrile  period  and  diminishes  at  the  end  of  the 
infection,  at  the  time  when  the  temperature  falls  below  the  normal. 
Nevertheless,  it  is  always  advisable  to  combat  excessive  elevation  of 
temperature  as  well  as  hypothermia.  It  is  here  that  the  use  of  baths 
is  indicated — cold  baths  in  the  former  instance,  warm  baths  in  the 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  759 

latter.   They  re-establish  the  organic  combu  tiom  and  bring  them  to 
the  rate  which  is  favorable  for  glycogenosis. 

The  second  condition  which  modifie  glycogen©  i  i  of  still  greater 
importance.  We  refer  to  starvation.  Claude  Bernard  long 
demonstrated  that  glycogenosis  is  diminished  in  animals  deprived  of 
food.  We  have  learned  that,  under  the  same  conditions,  the  pro- 
tective r61e  of  the  liver  againsl  poisons  and  microbes  i  weakened. 
These  facts  demonstrate  thai  it  is  indispensable  to  nourish  infected 
individuals.  They  are  qo  longer  deprived  of  aliments,  and  are  gener- 
ally given  milk,  sometimes  bouillon  or  oilier  lighl  nourishment.  The 
author  believes  that  warm  beverages  containing  sugar  produce,  from 
this  point  of  view,  a  very  favorable  effect.  The  sugar  furnishes  the 
most  important  element  for  glycogenesis.  The  patienl  should  not. 
therefore,  be  deprived  of  it.  It  would  even  be  better,  perhaps,  to 
utilize  grape  sugar  instead  of  cane  sugar.  In  fact,  saccharose  must 
be  converted  before  it  can  serve  for  the  formation  of  glycogen  and 
the  nutrition  of  the  organism.  We  do  not  know  whal  the  activity 
of  the  invcrsive  intestinal  ferment  in  the  course  of  diseases  is.  It 
would,  therefore,  be  preferable  to  employ  glucose.  In  this  connec- 
tion honey  seems  to  the  author  clearly  indicated.  As  is  known,  it 
contains  from  65  to  75  per  cent,  of  glucose  and  from  2  to  8  per  cent. 
of  cane  sugar. 

In  recent  years  an  endeavor  has  been  made  to  increase  the  alimen- 
tation of  patients  suffering  from  fever.  These  attempts  will  be  dis- 
cussed in  connection  with  general  hygiene.  It  is  certain,  however, 
that  from  the  particular  point  of  view  occupying  us  the  method  i> 
of  incontestable  advantage.  The  importance  of  certain  elements  for 
the  defense  of  the  organism,  notably  carbohydrates,  should  not.  how- 
ever, be  exaggerated.  Experimental  investigations  pursued  by  us 
demonstrated  that  while  small  amounts  of  glucose  increase  the 
protective  action  of  the  liver  large  closes  diminish  it.  The  thera- 
peutic amount  of  glucose  may  be  said  to  be,  at  least  for  the  rabbit, 
3  grams  per  kilogram  of  animal,  and  8  or  10  grams  the  unfavorable 
amount.  If  these  results  were  applied  to  man.  from  ISO  to  200  grams 
of  glucose  should  be  administered  per  day  to  an  adult  weighing  60 
or  65  kilograms. 

It  is  not  only  feeding  that  assures  the  function  of  the  liver :  thera- 
peutics furnishes  us  a  valuable  agent — ether.  As  in  the  case  of  sugar, 
however,  the  effects  of  ether  vary  with  the  amount  administered. 
In  animals,  0.4  c.cm.  of  ether  per  kilogram  of  animal  increases  con- 


760  IXFECTIO  US  DISEASES. 

siderably  the  action  of  the  liver;  1  com.  abolishes  it.  Subcutaneous 
injection  of  ether  produces  a  favorable  action;  but  the  best  effects 
are  obtained  by  ingestion.  In  this  case  the  substance  passes  directly 
to  the  liver,  and  at  the  same  time  stimulates  its  glycogenic  function 
and  its  action  upon  toxins  and  microbes.  The  application  of  these 
experimental  data  is  very  simple.  When  hepatic  insufficiency  or 
torpidity  is  suspected,  20  or  30  grams  of  syrup  of  ether  containing 
2  per  cent,  of  the  active  substance  should  be  prescribed  per  day. 
Stimulation  of  the  liver  may  possibly  be  obtained  by  other  medicines, 
but  no  accurate  data  are  as  yet  at  hand  bearing  upon  this  point. 
There  is  every  reason,  however,  to  suppose  that  purgatives  and  not- 
ably calomel,  and  perhaps  certain  cholagogues,  exert  a  favorable 
action.  More  importance  is  attached,  however,  to  a  procedure  which 
acts  mechanically.  We  refer  to  cool  enemas.  Their  action  is  double. 
The  cold  causes  the  vessels  of  the  large  intestine  to  contract  and,  by 
furnishing  the  liver  with  a  greater  amount  of  blood,  stimulates  its 
function.  On  the  other  hand,  water  is  absorbed  and  brought  first 
to  the  hepatic  gland.  As  the  activity  of  a  tissue  depends  upon  its 
richness  in  water,  when  fluid  is  furnished  to  an  organ,  it  thus  becomes 
supplied  with  the  element  which  is  indispensable  for  its  activity. 

To  sum  up,  we  may  increase  the  protective  role  of  the  liver  by 
feeding  the  patient,  by  prescribing  substances  which  stimulate  the 
activity  of  the  glandular  cells  and  by  administering  cold  enemas 
which  favor  the  circulation  of  the  portal  vein. 

Protective  Role  of  the  Lungs.  The  lungs  also  exert  considerable 
influence  upon  microbes  and  toxins.  The  conditions  which  may 
disturb  their  function  and  diminish  or  abolish  their  protective  action 
are  not  well  known.  This  much  is  proved,  viz.,  that  the  lungs  act 
only  when  oxidations  take  place  in  a  regular  manner.  The  author 
demonstrated  this  by  means  of  artificial  circulation,  and  Cafiero 
proved  the  same  by  causing  a  mechanical  dyspnea  in  living  animals. 
Inhalation  of  oxygen  should,  therefore,  be  prescribed  when  the 
lungs  are  altered  and  hematosis  is  poorly  carried  on.  It  is  true,  as 
was  proved  by  our  experimental  researches,  that  the  normal  lungs 
act  almost  in  the  same  manner,  whether  ordinary  air  or  pure  oxygen 
circulates  in  them.  When  the  lungs  are  altered,  however,  such  can 
no  longer  be  the  case,  and  the  excess  of  oxygen  which  is  brought  to 
them  must  compensate  for  the  diminution  of  the  field  of  hematosis. 

It  is  likewise  possible  to  stimulate  the  action  of  the  lungs  by  favor- 
ing the  circulation.    Cold  baths  are  well  calculated  to  accomplish  this 


THERAPEUTICS  OF  TNFECTI0U8  DISEASES.  70] 

end,  since  they  diminish  passive  pulmonary  conge  tion.  Cupping 
acts  in  the  same  way.  Certain  cardiac  medicine  may  al  o  be  pre- 
scribed, but  most  of  them  stimulate  particularly  the  left  ventricle, 
and  consequently  exert  bul  little  influence  upon  the  pulmonary 
circulation.  Under  these  circumstances  recourse  may  be  had  to  8 
method  which  h:is  been  found  efficient  by  clinical  observation  in 
cases  <»f  pulmonary  infections  -  thai  is,  blood-letting. 

The  Role  of  the  Blood.  It,  is  evidenl  thai  other  parte  of  the 
organism  must  likewise  serve  for  the  distribution  <>\'  microbes  and 
poisons.  Our  knowledge  of  this  subject,  however,  U  ae  yel  limited. 
particularly  as  regards  therapeutic  indications  of  practical  use.  The 
organs  and  (issues  as  well  as  (he  fluids,  and  notably  the  blood,  exercise 
a  protective  action  against-  infectious  agents.  Toxins  are  destroyed  by 
oxidation  in  the  blood  and  probably  also  in  the  intercellular  plasma. 
If  lesions  occur  in  the  respiratory  apparatus  it  is  necessary,  in  order  to 
insure  the  destruction  of  toxins,  to  resort  to  the  oxidizing  method. 
Inhalation  of  oxygen  is  then  indicated.  This  procedure  increases  the 
amount  of  oxygen  in  the  blood,  and  its  efficiency  is  further  demon- 
strated by  numerous  observations  and  experimental  facts.  Microbic 
poisons  as  well  as  those  of  cellular  origin  are  thus  annihilated.  In 
this  connection  it  is  well  to  remember  what  we  have  repeatedly 
stated,  namely,  that  oxidations  are  diminished  in  the  course  of  infec- 
tious diseases  and  typhoid  states.  There  is,  therefore,  every  reason 
for  intervention  in  all  these  cases.  Dr.  A.  Robin  advised  the  admin- 
istration of  benzoic  acid,  which  increases  oxidation  and  favors  elim- 
ination of  the  products  of  disassimilation  by  rendering  them  soluble. 
This  idea  seems  to  us  perfectly  correct.  We,  therefore,  prescribe 
from  2  to  4  grams  of  benzoate  of  soda  daily  in  grave  infectious 
states,  notably  when  the  lesions  of  the  liver,  lungs,  or  kidneys 
seem  to  hinder  the  evolution  or  elimination  of  the  toxic  products 
originating  from  disassimilation.  If  the  liver  is  at  the  same  time 
disturbed  we  prescribe  in  the  same  potion  with  70  grams  of  julep, 
4  grams  of  benzoate  of  soda  and  30  grams  of  syrup  of  ether;  a  table- 
spoonful  is  taken  every  hour.  Although  oxidation  is  a  general  pro- 
cedure of  attenuation  of  toxins,  a  by  no  means  less  important  role 
is  played  by  the  cells  which  are  capable  of  picking  up  and  digesting 
microbes  and  secreting  substances  which  diminish  their  activity  and 
neutralize  their  toxins.  The  therapeutist  must,  therefore,  endeavor 
to  stimulate  phagocytosis  and  favor  germicidal  and  antitoxic  secre- 
tions.   Unfortunately,  we  possess  but  little  information  on  this  sub- 


7 1 ! L>  INFEi  ■  Tl 0U&  D TSEASES. 

ject.  All  we  know  is  that  injections  of  artificial  serum  give  rise 
to  an  abundant  proliferation  of  the  cells  of  the  bone-marrow.  The 
latter  tissue  furnishes  the  economy  with  the  greatest  part  of  the 
leucocytes  charged  with  the  function  of  defense.  Hence  it  is  not 
difficult  to  understand  the  excellent  effects  of  these  therapeutics  in  all 
cases  in  which  the  reactions  of  the  organism  seem  to  be  insufficient. 
Role  of  the  Emunctories.  After  undergoing  in  the  organism  a 
series  of  transformations,  the  toxic  substances  are  eliminated  through 
the  various  emunctories.  Some  of  them  pass  into  the  stomach; 
others,  notably  the  poisons  of  the  colon  bacillus,  are  thrown  into  the 
intestine.  Their  elimination  may,  therefore,  be  hastened  by  lavage  of 
the  alimentary  canal.  The  kidneys,  however,  are  the  principal  route 
of  elimination.  It  must  be  remembered  that  in  the  course  of  infec- 
tions the  urinary  secretion  is  diminished,  and  in  general  the  toxicity 
of  the  urine  is  also  lessened.  The  physician  must  endeavor  to  favor 
diuresis.  For  this  purpose  the  patients  must  be  given  plenty  of 
water,  also  enemas  which  they  may  retain,  at  least  in  part.  When 
necessary,  salt-water  may  also  be  injected  beneath  the  skin.  A 
second  indication  is  drawn  from  the  state  of  the  blood  pressure. 
With  the  assistance  of  Dr.  Gamier,  the  author  has  found  in  several 
cases  of  scarlatina  that  when  the  urinary  secretion  is  very  scant,  and 
especially  when  temporarily  suppressed,  the  blood  pressure  rises;  the 
heart,  by  the  energy  of  its  contractions,  seems  to  strive  to  overcome 
the  renal  barrier.  On  the  basis  of  this  fact,  the  physician  must 
endeavor  to  still  raise  the  blood  pressure.  Certain  medicines  may 
accomplish  this  end.  It  is  better,  however,  to  resort  to  cold  baths. 
In  patients  constantly  treated  by  baths  the  renal  secretion  becomes 
profuse,  and,  as  is  demonstrated  by  the  study  of  urinary  toxicity,  it 
carries  off  noxious  substances.  The  elimination  thus  being  carried 
on  during  the  entire  course  of  the  disease,  the  mode  of  its  termination 
is  often  modified.  Such  is  notably  the  case  in  pneumonia  in  which 
the  urinary  crisis,  which  is  no  longer  any  raison  d'etre,  is  not  pro- 
duced. Another  cause  disturbing  diuresis  is  the  fact  that  the  excre- 
mentitious  substances  are  not  sufficiently  oxidized.  In  this  connec- 
tion, cold  baths  exercise  a  favorable  action  which,  as  already  stated, 
may  be  completed  by  the  administration  of  sodium  benzoate.  This 
medicine  is  likewise  to  be  resorted  to  when  lesions  of  the  kidneys 
hinder  the  function  of  these  organs.  It  would  then  be  useless  to 
prescribe  diuretics,  which  would  only  increase  the  lesions  by  stimu- 
lating the  cells  which  are  already  diseased. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

When  infectious  nephritis  is  too  intense  or  exten  ive,  it.  will  be 
necessary  to  diminish  intoxication  by  stimulating  elimination  through 
other  channels,  notably  by  the  digestive  trad  and,  in  gra 
by  blood-letting.    The  author  does  not  trust  much  in  the  vicarious 
role  of  sweating.    Nevertheless,  in  certain  disea  e  .  thi  eems 

to  throw  out  toxic  substances.  In  several  cases  of  diphtheria  treated 
by  subcutaneous  injections  of  pilocarpine  we  noticed,  in  consequence 
of  sweating,  very  great  amelioration  in  the  general  state.  It  would, 
therefore,  be  worth  while  fco  take  up  this  study  and  to  learn  whether 
the  old  therapeutics,  which  treated  fever  patients  by  giving  them 
hot  drinks,  diaphoretics,  and  by  covering  them  heavily,  did  in  cer- 
tain cases  yield  good  results  through  the  sweating  thus  produced. 

The  secretions  of  the  organism  at  times  eliminate  morbid  produc- 
tions resulting  from  microbic  action  or  a  reaction  of  the  economy. 
Thus,  the  pseudomembranes  of  diphtheria  localize  infection  and 
oppose  penetration  of  the  microbe  and  its  toxins  into  the  economy. 
The  organism  has  done  well  in  producing  these  pseudomembranes, 
but  it  will  be  equally  advantageous  for  it  to  eliminate  them  at  a 
certain  period  of  evolution.  Hence,  it  strives  to  detach  them  by 
means  of  a  secretion  of  the  subjacent  glands  and  by  increased  activity 
of  the  salivary  glands.  It  is  easy  to  stimulate  this  process  by  admin- 
istering sialagogues  and  notably  pilocarpine.  The  action  of  this  medi- 
cine upon  the  heart  is  much  dreaded.  It  must,  therefore,  be  em- 
ployed with  caution.  In  adults,  however,  the  author  has  obtained 
excellent  results  from  its  employment  in  the  treatment  of  pseudo- 
membranous anginas  and  particularly  diphtheritic  sore  throat.  He 
prescribes  a  subcutaneous  injection,  morning  and  evening,  of  10 
drops  of  a  1  per  cent,  solution  of  nitrate  of  pilocarpine.  In  twenty- 
four  or  forty-eight  hours  the  pseudomembranes  are  detached  and  the 
patient  experiences  a  very  notable  improvement  in  his  general  state. 

Sialagogues  may  also  be  employed  in  all  sorts  of  buccal  infections. 
The  one  most  frequently  used  is  chlorate  of  potash,  which  is  admin- 
istered in  daily  doses  of  from  2  to  4  grams.  The  action  of  this  medi- 
cine is  admittedly  due  to  its  passage  into  the  saliva.  The  amount 
eliminated  through  this  channel,  however,  is  quite  small;  it  amounts 
to  hardly  3  per  cent.  It  is  to  be  recognized,  however,  that  in  this 
case  the  local  treatment  has  more  influence  than  the  salivary  exci- 
tation. 

Medication  is  also  physiological  when  the  elimination  undertaken 
by  the  organism  is  stimulated  by  the  employment  of  the  same  pro- 


764  INFECTIOUS  DISEASES. 

cecfures  utilized  by  the  economy  itself.  Bronchial  and  pulmonary 
lesions  result  in  expectoration  calculated  to  throw  out  the  exudates, 
the  signification  of  which  is  exactly  the  same  as  that  of  pseudomem- 
branes  in  diphtheria.  Physiological  medication  consists  in  prescrib- 
ing expectorants.  These  are  divided  into  two  groups,  according  as 
they  act  by  increasing  the  force  with  which  the  bronchi  throw  out 
their  contents  or  by  modifying  the  exudate  of  the  respiratory  appa- 
ratus. Emetics  act  mechanically.  A  second  group  contains  expec- 
torants. The  most  important  expectorants  are  those  which  liquefy 
the  exudates.  The  first  among  them  is  chlorohydrate  of  ammonia, 
an  excellent  medicine,  which  is  to  be  given  to  children  in  half-gram 
doses  daily,  and  from  2  to  4  grams  to  adults.  It  may  be  combined 
with  the  salts  of  antimony.  White  oxide  of  antimony  seems  to  the 
author  by  far  the  better  preparation,  provided  it  is  not  employed  in 
too  strong  doses.  The  author  has  obtained  excellent  results  by  giving 
20  eg.  to  30  eg.  a  day.  It  is  an  insoluble  salt  which  may  be  given 
in  water.  If  emetics  are  given  in  small  doses  so  as  to  avoid  vomiting 
and  nausea,  they  act  as  expectorants.  Ipecacuanha  may  thus  be 
prescribed  in  fractional  doses :  apomorphine,  1  mg.  every  hour  in  the 
form  of  pills  or  in  a  potion.  For  example,  one  may  prescribe  as 
follows : 

Crystallized  hydrochlorate  of  apomorphine     .  0.01  centigram  (£  grain). 

Hydrochlorate  of  morphine 0.03  "  (£  grain). 

Hydrochloric  acid 3        drops. 

Simple  S3Tirp 30      grams  (gj). 

Water 90  "       (giij). 

Lastly,  the  syrup  of  polygala  seems  to  belong  to  this  group,  but 
it  should  not  be  employed  if  there  is  fever  or  digestive  disorders. 

Physiological  medication  is  applicable  to  a  great  number  of  gastro- 
intestinal disorders.  When  the  gastric  disturbances  give  rise  to 
nausea,  an  emetic  is  called  for  in  order  to  achieve  the  work  begun 
by  nature  by  ejecting  the  substances  which  encumber  and  hurt  the 
gastric  cavity.  Likewise,  in  patients  suffering  from  diarrhea,  which 
expresses  a  natural  therapeutic  tendency,  excellent  results  are  often 
obtained  by  prescribing  a  purgative.  On  the  other  hand,  in  certain 
cases  it  is  advisable  to  increase  constipation;  in  peritonitis  and  in 
intestinal  hemorrhage  the  movements  of  the  bowels  may  intensify 
the  disorders.  It  is,  therefore,  desirable  to  immobilize  the  digestive 
tract.  For  this  purpose  opium  is  mostly  prescribed  in  the  form  of  the 
extract,  1  eg.  every  hour. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  766 

In  brief,  such  are  the  various  medicines  which  may  \»-  emplo 
when  we  wish  to  practise  physiological  medication.     All  of  them 
increase  certain  morbid  manifei  fcation  ,  or,  more  exactly,  they  I 
fche  reactions  which  the  organism  calls  into  play  in  order  to  combat 
microbes  and  I  heir  toxins. 

Reactions  are  not  always  »>f  the  desirable  kind,  however.  In  a 
great  many  cases  they  may  give  rise  to  new  derangements  by  their 
intensity  and  persistence.  They  iniisi  then  be  combated.  This 
would  be  contra-physiological  medication,  the  indication):  and  pro- 
cedures of  which  will  be  discussed  in  connection  with  symptomatic 
therapeutics. 

Treatment  of  Inflammatory  Manifestations. 

If  it  were  possible  in  every  case  to  attack  the  cause  of  the  disturb- 
ances, the  treatment  of  inflammatory  manifestations  would  always 
draw  its  indications  from  etiology.  Antiseptic  medication,  when 
applicable,  responds  to  this  indication.  When  the  cause  cannol  be 
reached,  and  it  is  impossible  to  act  upon  the  mechanism  which  engen- 
ders the  morbid  phenomena,  it  is  necessary  to  resort  to  physiological 
medication.  In  all  cases  of  inflammation  two  series  of  phenomena 
are  to  be  taken  into  account:  those  which  occur  at  the  diseased  gj  ol 
and  require  local  treatment,  and  those  which  result  from  distui  1  lances 
engendered  by  the  primary  lesion  in  other  parts  of  the  organism  and 
require  general  treatment. 

Local  Treatment.  Local  treatment  may  be  directed  either  to 
moderate  or,  on  the  contrary,  to  stimulate  and  increase  inflammatory 
manifestations.  In  the  former  case  the  method  is  called  antiphlo- 
gistic. Now,  if  we  take  up  the  four  cardinal  phenomena  of  inflam- 
mation, we  shall  see  that  each  of  them  may  quite  readily  be  com- 
bated or  stimulated. 

Hot  Applications.  Let  us  first  consider  heat.  Increase  in  local  tem- 
perature indicates  increased  activity  in  nutritive  exchanges,  which 
augments  the  production  of  heat.  At  the  same  time,  as  may  readily 
be  noticed  hy  applying  the  hand  to  the  diseased  spot,  there  is  in- 
creased dissipation  of  heat.  Exaggeration  of  metabolism  brings 
about  a  more  marked  vascularization,  whence  the  second  phenom- 
enon, redness. 

In  the  presence  of  these  two  symptoms  the  therapeutist  may  think 
it  advisable  to  stimulate  inflammation.  He  resorts  to  hot  applica- 
tions.   He  thus  acts  upon  the  production  of  heat  and.  it  seems,  he 


766  INFECTIOUS  DISEASES. 

practises  naturalistic  therapeutics.  It  is  to  be  noted,  however,  that 
by  this  local  treatment  he  imperfectly  imitates  nature,  for  it  hinders 
the  second  phenomenon — i.  c,  increased  radiation.  If,  for  example, 
the  diseased  part  be  immersed  in  very  hot  water,  or  if  hot  compresses 
be  applied,  the  temperature  is  evidently  increased,  but  radiation 
diminishes.  -  Nevertheless,  this  method  yields  good  results.  It  is 
utilized  especially  in  cutaneous  inflammations.  In  the  treatment  of 
erysipelas  the  author  applies  upon  the  affected  parts  compresses  of 
gauze  clipped  either  in  hot  water  or  some  weak  infusion.  Such  com- 
presses should  not  be  allowed  to  become  cold,  for  the  evaporation  of 
the  water  dissipates  the  heat  and  produces  a  contrary  result.  Hot 
poultices  have  the  advantage  of  better  preserving  heat,  and  may  be 
prescribed  under  the  same  circumstances.  In  order  to  avoid  the 
inconvenience  resulting  from  evaporation  or  moisture,  the  diseased 
part  may  be  surrounded  with  rubber  tubes  in  which  hot  water  is 
circulated.  It  is  likewise  possible,  in  the  case  of  the  abdomen,  to  place 
upon  the  part  rubber  bags  filled  with  hot  water.  When  treating  the 
extremities  one  may  employ  for  the  same  purpose  small  bags  filled 
with  sand,  which  may  be  placed  under  and  around  the  limbs,  while 
the  upper  surface  may  be  covered  with  a  bag  of  hot  oatmeal  in  order 
to  avoid  too  much  weight.  Lastly,  when  the  lesion  is  well  circum- 
scribed, hot  air  may  be  employed,  as,  for  example,  in  the  case  of  soft 
chancre. 

Refrigeration.  Refrigeration  may  be  accomplished  by  application 
of  cold  compresses  or  poultices,  by  circulation  of  cold  water  in  tubes, 
by  cold  air  and  application  of  bags  filled  with  water  or  ice.  When 
an  ice-bag  is  employed  a  flannel  should  be  interposed  between  the 
bag  and  the  skin  in  order  not  to  hurt  the  skin.  This  method  evidently 
increases  radiation  and  diminishes  heat ;  on  the  other  hand,  it  gives 
rise  to  vasoconstriction,  which  causes  the  second  cardinal  phenome- 
non— i.  e.,  heat — to  disappear.  This  method  is  hardly  ever  applicable 
to  superficial  lesions.  Inflammations  of  the  skin,  of  subcutaneous 
tissue,  and  of  lymphatic  glands  should  not,  as  a  rule,  be  treated  by 
means  of  refrigeration.  These  inflammations  already  have  a  certain 
tendency  to  sphacelation,  which  would  be  increased  by  cold.  Brown- 
Sequard  believed  that  cold  and  hot  applications  should  be  used 
alternately;  the  reverse  modifications  which  are  thus  produced  in  the 
vessels  hinder  the  production  of  gangrene.  The  author  believes  that 
heat  is  sufficient  for  this  purpose. 

The  refrigerating  method,  on  the  contrary,  renders  immense  service 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  767 

in  the  treatment  of  deep  inflammations.  In  acute  inflammatioi 
the  abdominal  organs,  in  appendicitis,  peritonitis,  and  periuterine 
lesions  remarkable  results  are  obtained.  Likewi  e,  the  application 
of  an  ice-bap;  upon  the  precordial  region  or  upon  the  cranium  is 
classical  in  cases  of  inflammation  of  the  pericardium  or  menii 
respectively.  The  author  employs  the  same  method  when,  in  the 
course  of  otitis,  he  finds  Bymptoms  of  mastoiditis.  The  appli- 
cation of  the  ice-bag  upon  the  mastoid  region  succeeded,  in  several 

cases,  in  arresting  the  accidents.    It  must  be  home  in  mind,  how 
that  care  should  be  taken  not  to  allow  the  bag  to  grow  warm.    When 
the  ice-bag  is  used  it  must  be  renewed  from  time  to  time. 

Cold  may  likewise  he  employed  to  assuage  the  third  cardinal 
phenomenon — pain.  It  produces  very  marked  sedation  and  acts 
upon  the  pain  of  mastoiditis  or  osteomyelitis  as  well  as  upon  that  of 
orchitis.  The  action  of  cold  is  complex.  Besides  the  waste  of  heat, 
cold  causes  constriction  of  the  bloodvessels.  Not  only  the  small 
arteries  of  the  skin  but  also  those  of  the  deeper  parts  become  con- 
stricted. The  experiments  of  F  m  lericq  leave  no  doubt  in  i  hi-  regard. 
The  application  of  the  ice-bag  upon  the  cranium  produces  constric- 
tion in  the  cutaneous  and  meningeal  arteries.  The  latter  are  too 
rapidly  reached  to  permit  the  supposition  that  the  phenomenon  is 
due  to  the  propagation  of  cold;  it  is  probably  a  process  of  reflex  vaso- 
constriction. 

Moreover,  cold  increases  the  tonicity  of  the  vascular  muscles  as 
well  as  those  of  the  myocardium.  The  latter  result  has  considerable 
importance.  Application  of  the  ice-bag  over  the  region  of  the  heart 
may  be  prescribed  in  all  cases  of  myocarditis  whenever  it  is  necessary 
to  render  the  function  of  the  organ  more  regular  and  energetic. 

Immobilization.  Every  inflammatory  lesion  causes  pain  and  swell- 
ing which  disturb  considerably  the  function  of  the  affected  parts. 
The  patient  instinctively  immobilizes  himself  as  much  as  possible. 
Rest  of  the  inflamed  parts  is  one  of  the  best  therapeutic  measures. 
It  is  constantly  resorted  to  in  surgery.  The  application  of  splints 
and  apparatus  is  designed  to  prevent  every  movement  of  the  inflamed 
parts,  and  thus  complete  the  natural  work.  In  certain  cases  it  is 
possible  to  arrest  the  inflammatory  swelling  by  means  of  a  methodic 
compression;  but  this  latter  method  is  hardly  ever  indicated  in  c  -  - 
of  acute  inflammation.  The  results  obtained  by  submitting  inflamed 
parts,  and  notably  the  skin  affected  by  erysipelas,  to  the  elastic 
compression  of  a  layer  of  collodion  have  not  been  encouraging. 


INFECTIOUS  DISEASES. 

Compression  may  be  useful  by  hastening  the  absorption  of  exudates 
only  after  the  acute  phenomena  have  passed  away. 

Depletion.  Inflammatory  congestions  and  exudations  are  often 
combated  by  depletion.  Scarifications  upon  the  diseased  parts  are 
useful,  as  they  permit  the  discharge  of  a  small  amount  of  blood  or 
serosity.  thus  relieving  considerably  the  painful  tension  of  which  the 
patient  complains.  Some  have  even  attempted  to  arrest  the  progress 
of  certain  inflammations  in  this  manner.  Thus,  scarifications  have 
sometimes  been  practised  upon  an  erysipelatous  patch.  The  pro- 
cedure does  not  seem,  however,  to  have  given  satisfactory  results. 

Revulsion.  Revulsion  is  often  practised  upon  the  region  of  the  skin 
corresponding  to  the  diseased  organ  as  well  as  in  distant  parts.  Dry 
or  scarified  cupping  of  the  precordial  region  and  sometimes  applica- 
tion of  leeches  are  often  prescribed  in  cases  of  acute  inflammation  of 
the  cardiac  muscle  and  especially  of  the  serous  membranes.  The 
same  means  are  applied  in  the  treatment  of  pleuropulmonary  and 
abdominal  inflammations ;  or,  instead  of  these  mechanical  procedures 
irritating  substances,  such  as  mustard  poultices,  friction  with  croton 
oil,  and  application  of  certain  plasters  may  be  prescribed.  In  other 
cases  applications  are  made  to  distant  parts.  In  cases  of  thoracic 
or  cerebral  inflammation  revulsion  is  effected  by  cupping  the  extremi- 
ties, applying  leeches  to  the  anus  or  mustard  plasters  upon  the  legs. 
In  the  conception  of  the  ancient  practitioners,  all  these  medications 
had  the  same  object.  They  were  intended  to  draw  the  inflammation 
of  the  diseased  organ  toward  those  parts  of  the  organism  where  it 
would  cause  no  harm.  Such  was  the  idea  of  Hippocrates,  who  prac- 
tised revulsion,  and  in  this  manner  proposed  to  draw  away  the 
humors  which  threatened  to  attack  an  important  organ.  Most 
modern  therapeutists,  instead  of  the  humoral  hypothesis  of  revulsion, 
hold  the  nervous  theory  to  be  true.  They  admit  that  excitation  at 
one  point  causes,  by  means  of  inhibitory  acts,  palliation  of  congestive 
and  inflammatory  phenomena  occurring  in  another  part  of  the  econ- 
omy. The  revulsive  application  calls  into  play  the  sensory  system, 
and  coincidently  it  produces  a  series  of  circulatory  modifications. 

Among  the  revulsives,  some,  like  sinapisms,  cause  congestion  in 
the  skin,  and  thus  modify  the  water  content  of  the  blood.  Others 
produce  extravasation  of  a  quantity  of  blood ;  such  is  the  case  in  dry 
cupping.  Still  others  produce  local  blood-letting.  In  the  last-named 
case,  between  the  superficial  and  the  profound  circulation  a  balancing 
is  admitted.    The  effect  is  deeper,  however,  and  the  flow  of  blood 


THEEAPEUTI08  OF  INFECTIOUS  DI8EA8E8.  769 

may  relieve  the  venous  system.    To  this  end  blood  letting  should  be 

practised  at  a,  determined  point.     Thus,  in  order  to  'liinini  h  pa 

congestion  of  the  brain,  leeches  must  be  applied  upon  Hi''  ma 
processes.    When  action  upon  the  liver  is  desired,  they  are  placed 
about  the  anus  or  even  upon  the  anal  mucous  membrane.    Hepatic 
depletion  is  explained  by  the  vascular  connections  which  unite-  t|,i- 
region  to  the  portal  system. 

In  brief,  revulsion  seems  to  acl  in  two  ways:  by  producing  deple- 
tion of  blood  and  a  reflex  excitation,  expressed  by  an  inhibitory 
action  upon  the  inflamed  part.  Ii  is  probably  owing  to  nervous  con- 
nections between  the  superficial  and  deeper  parts  of  a  region  thai 
revulsion  is  effected,  preferablyin  the  pari  corresponding  to  the  dis- 
eased organ.  This  mode  of  excitation  belongs  to  all  revulsives, 
because  all  produce  excitation  of  the  nerve  terminations.  Some  <  i 
them  also  give  rise  to  circulatory  modifications  by  inducing  conges- 
tion, ecchymoses,  or  depletion.  In  the  latter  case  ;i  general  modifi- 
cation in  the  blood  is  produced  in  addition  to  the  local  change.  The 
remarkable  effects  of  local  depletion  are  not,  however,  to  be  attrib- 
uted to  the  latter  result.  All  scarified  cuppings  applied  to  the  pre- 
cordial region  do  not  act  like  general  blood-letting.  It  is,  therefore, 
probable  that  there  is  a  harmony  in  the  vascular  or  vasomotor  system 
of  the  same  segments  of  the  body.  A  modification  produced  in  the 
local  circulation  of  one  part  of  the  segment  must  affect  preferably 
and  in  a  special  manner  the  subjacent  parts.  Whatever  be  the 
theoiy,  the  practical  importance  of  revulsion  is  undeniable.  It  is 
resorted  to  in  two  cases,  namely,  at  the  beginning  of  inflammation 
and  at  its  terminal  period. 

At  the  beginning  the  immediate  result  of  revulsion  is  frequently 
to  assuage  one  of  the  elements  of  inflammation  to  which  we  have  thus 
far  hardly  referred,  viz.,  pain.  The  pain  in  the  side  felt  in  pneu- 
monia rapidly  yields  to  a  few  dry  cuppings  and  still  more  readily  to 
scarified  cuppings.  The  same  is  true  of  the  painful  distress  of  patients 
suffering  from  acute  pericarditis.  At  the  same  time  the  congestive 
phenomena  are  rapidly  palliated  and,  consequently,  the  inflamma- 
tion is  relieved.  It  may  be  objected  that  inflammatory  reaction  is 
of  secondary  importance  and  that  there  is  no  advantage  in  combating 
it.  This  remark  would  be  perfectly  exact  if  the  organism  always  pro- 
portioned its  efforts  to  its  needs.  As  we  have  time  and  time  again 
remarked,  however,  slight  causes  often  produce  extremely  violent 
reactions.    We  may  recall,  for  example,  a  benign  cutaneous  lesion. 

49 


770  IXFECTIO  US  DISEASES. 

such  as  furuncle.  Around  the  small  lesion,  which  must  arrest  and 
destroy  the  staphylococcus,  an  edema  develops  which  sometimes 
assumes  enormous  proportions.  When  the  seat  of  the  phenomenon 
is  the  skin  no  great  harm  results;  but  if  the  process  occurs  in  a  vital 
organ. like  the  heart,  the  diffusion  of  the  lesion  may  have  fearful 
consequences.  Hence,  revulsion  is  necessary,  and  it  is  the  more  useful 
as  the  affected  part  occupies  a  higher  rank  in  the  organic  hierarchy. 

Revulsion  is  likewise  employed  at  the  end  of  the  morbid  evolution 
when  recovery  is  tedious.  In  this  case  depletive  measures  are  not 
resorted  to ;  but  excitants,  such  as  sinapisms,  vesicatories,  and  ther- 
mal cauterizations  are  applied.  By  excitation  of  the  nerve  ends  we 
bring  about  increased  nutritive  activity  of  the  parts  which  are  oper- 
ated upon  and  those  which  are  subjacent. 

We  thus  arrive  at  the  conclusion  that  revulsion  is  not  compre- 
hensible unless  we  admit  a  nervovascular  synergy  establishing  a 
morbid  sympathy  in  the  various  segments  of  the  body.  According 
to  this  view,  it  is  intelligible  why  revulsion  practised  upon  the  spinal 
column  influences  the  viscera.  While  certain  parts  possess  a  relative 
autonomy,  all  are  united  by  numerous  synergies.  Hence,  it  is  con- 
ceivable that  a  local  modification  may  produce  extensive  effects. 
It  is  for  this  reason  that  we  may  act  upon  a  thoracic  organ  by  apply- 
ing revulsives  to  the  lower  extremities. 

In  the  beginning  of  all  local  inflammations  local  revulsion  must 
be  practised.  The  choice  of  the  revulsive  varies  with  the  age  and 
state  of  the  individual.  In  young  children  we  have  often  to  treat 
pleuropulmonary  inflammations.  We  must  resort  to  mustard  poul- 
tices and  baths,  and  envelop  the  patient  with  moist  sheets.  It  is 
to  be  borne  in  mind  that  blood-letting,  even  of  a  local  character,  is 
not,  as  a  rule,  well  borne  by  children.  In  the  case  of  vigorous  adults, 
scarified  cupping  represents  the  best  method  of  taking  blood.  In 
debilitated  subjects  and  delicate  women  milder  revulsives,  such  as 
dry  cupping,  sinapisms,  must  generally  be  resorted  to  and,  in  graver 
cases,  thermocauterization.  Intervention  must  be  more  energetic 
the  more  important  or  delicate  the  affected  part.  Cardiac  and  cere- 
bromeningeal  manifestations  thus  require  the  promptest  intervention . 

When  chronic  lesions  are  to  be  dealt  with,  thermocauterization, 
vesicatories,  and  at  times  simply  application  of  tincture  of  iodine,  are 
employed.  An  abscess  (Vabc&s  par  fixation)  produced  by  means  of 
a  subcutaneous  injection  of  turpentine  is  a  method  related  to  the 
group  of  revulsive  procedures.    Its  mode  of  action  has  been  discussed. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  77] 

Some  authorities  contend  thai  the  circulating  bacteria  are  attracted 
to  the  abscess,  others  admit  a  modification  produced  in  the  phago- 
cytes and  hematopoietic  organs.  This  method,  firsl  employed  in 
puerperal  U'.vcv,  then  in  various  septicemias,  ha   been  utilized  with 

success  in  the  treatment  of  grave  pneumonias. 

Vasomotor  and  Depletive  Medications. 

We  have  thus  far  reviewed  the  methods  which  acl  locally  upon 
inflamed  parts.  There  are,  however,  other  modes  of  treatment  which 
modify  the  general  state.    The  therapeutisl  may  have  two  object* 

in  view:  to  stimulate  or  attenuate  inflammatory  manifestations.  In 
the  former  instance  he  employs  vasodilators,  and  administers,  for 
example,  trinitrin,  or  causes  the  patienl   to  inhale  nitrite  of  amyl. 

We  often  resort  to  the  first  of  these  medicines  in  the  Ireatmcnl  of 
erysipelas.  In  certain  cases  characterized  by  a  tedious  course  and 
lingering  resolution,  truly  interesting  results  are  obtained.  Inhala- 
tion of  amyl  nitrite  has  been  employed  by  Dr.  Hayem  in  the  treat- 
ment of  pneumonia. 

On  the  other  hand,  when  it  is  desired  to  check  the  inflammatory 
phenomena,  ergotin  or  tartar  emetic  is  sometimes  prescribed  accord- 
ing to  the  method  of  Rasori.  The  latter  medicine  is  employed  espe- 
cially in  pneumonia.  When  the  individual  is  vigorous  and  the  con- 
gestion is  extreme,  from  10  eg.  to  20  eg.  of  it  is  prescribed  in  a  potion 
of  120  grams  (lj-  grains  to  3  grains  in  4  ounces);  a  tablespoonful  is 
given  every  two  hours. 

Another  method  consists  in  combating  inflammation  by  means  of 
general  depletion.  Two  procedures  are  at  our  disposal :  we  may  give 
rise  to  a  serous  exudation,  and  for  this  purpose,  purgatives  and  dras- 
tics are  prescribed.  This  medication  is  alike  evacuative  and  revul- 
sive, as  it  not  only  causes  depletion  but  intestinal  irritation  as  well. 
All  inflammations  do  not  require  this  method.  It  is  indicated  par- 
ticularly in  meningeal  and  cerebral  inflammations.  Calomel  is  pref- 
erably employed.  In  adults  this  substance  is  administered  in  doses 
of  from  |-  gram  to  1  gram  (8  to  15  grains)  divided  into  three  powders 
and  given  at  intervals  of  fifteen  minutes.  In  children  from  10  eg.  to 
30  eg.  (1^  to  5  grains)  are  prescribed;  15  or  20  grams  (half  an  ounce | 
of  castor  oil  is  given  the  following  day.  This  is  the  classical  practice 
in  England,  and  is  to  be  recommended.  A  last  therapeutic  means 
consists  in  producing  depletion  by  blood-letting.  In  view  oi  the  im- 
portance of  this  method,  we  shall  devote  to  it  a  special  chapter. 


772  INFECTIOUS  DISEASES. 

Having  studied  inflammation  and  its  treatment  in  a  general  man- 
ner, it  now  remains  to  consider  the  therapeutics  of  its  various  con- 
sequences.   We  shall  begin  with  the  study  of  exudates. 

Treatment  of  Inflammatory  Exudates. 

Treatment  of  Serous  Exudates.  When  inflammatory  exudates 
acquire  a  certain  volume  or  occupy  an  important  organ  or  tissue, 
they  require  treatment  varying  according  to  their  seat  and  nature. 
Then  nature  may  be  serous,  pseudomembranous,  purulent,  or  putrid. 

The  serous  exudates  exert  upon  the  pathogenic  microbes  a  germi- 
cidal influence  and,  consequently,  represent  a  salutary  reaction.  It 
wall  suffice,  for  example,  to  recall  variola.  In  its  confluent  forms 
the  edematous  swelling  of  the  face  and  hands  constitutes  an  excellent 
sign  of  prognosis.  In  certain  cases,  however,  the  effusion  takes  place 
in  an  important  organ  or  a  delicate  tissue.  It  may  then  have  two 
inconveniences :  at  times,  owing  to  its  large  volume,  it  acts  mechani- 
cally and  hinders  the  regular  function  of  the  organ.  At  other  times 
it  separates  superficial  parts  from  deeper  layers,  and  thus  embarrasses 
their  circulation  and  nutrition,  and  may  even  cause  their  mortifica- 
tion. In  a  more  advanced  degree  the  exudate,  instead  of  being  simply 
diffuse,  predominates  at  one  point.  It  may  then  raise  the  skin  or 
the  mucous  membrane,  producing  bullae  or  phlyctenular.  This  is 
what  occurs  in  the  most  varied  affections,  such  as  herpes,  varicella, 
erysipelas,  pemphigus,  etc.  When  a  serous  cavity  is  adjacent  to  the 
inflamed  part  the  fluid  naturally  flows  into  it.  Pleurisies,  peritonites, 
pericardites,  meningites,  vaginites,  and  arthrites  which  are  the  equiv- 
alents of  edemas  and  bulla;,  are  thus  produced.  The  disposition  of 
the  tissues  being  more  favorable  for  the  free  flow  of  the  fluids,  the 
latter  exude  in  greater  profusion. 

The  effusion  taking  place  in  a  serous  membrane  likewise  represents 
a  germicidal  exudate.  Its  relations  to  the  subjacent  organs,  how- 
ever, produce  a  certain  number  of  functional  disturbances  and  sug- 
gest some  interesting  therapeutic  indications.  Thus  a  pleurisy,  on 
account  of  its  abundance,  may  embarrass  pulmonary  hematosis  and 
give  rise  to  progressive  asphyxia,  and  even  cause  sudden  death.  In 
face  of  these  dangers  the  question  is  whether  the  exudate  is  to  be 
respected  on  account  of  its  advantages.  By  compressing  the  lungs 
and  restricting  their  expansion,  by  hindering  their  function,  the  effu- 
sion checks  their  activity  and  condemns  these  organs  to  a  state  of 
relative  rest,  or  it  brings  about  immobilization  recalling  that  which 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  11?, 

the  physician  practises  upon  a  diseased  joint.  The  problem  Hum 
becomes  highly  complex.  If  would  be  equally  rational  to  argue  thai 
the  off  union,  l>y  restricting  pulmonary  activity,  hinder)  hemato  i  . 
and  consequently  disturbs  the  entire  organism.  On  the  other  hand, 
it  may  l>e  contended  thai  the  effusion  aecea  itatei  a  relative  re  I  on 
the  part  of  the  diseased  lung,  and  thus  favors  cicatrization  of  the 
lesion.  The  interest  of  this  discussion  is  do1  merely  one  of  pecula- 
tion; on  the  contrary,  it  guides  therapeutics,  [f  the  bad  effed 
thought  to  overbalance  the  advantages,  early  iuifrvniion  i-  n<-<-<:— 
sary  to  evacuate  the  fluid  by  thoracentesis.  On  (he  other  hand,  the 
physician  should  tiol  intervene  unless  the  effusion,  owing  to  it-  greal 
abundance,  threatens  to  produce  grave  disorders.  Even  then,  how- 
ever, evacuation  of  only  a  small  amount  of  the  exudate  will  suffice, 
because  complete  evacuation  is  often  followed  by  a  too  energetic  flux 
of  the  blood  into  the  previously  compressed  vessels,  am  I  a  consequent 
intense  congestion.  It  is,  therefore,  almost  universally  agreed  thai 
the  operation  should  not  be  performed  during  the  acute  stage.  The 
intervention  is  to  take  place  after  the  effusion  has  become  stationary. 
If  the  fluid  tends  to  be  absorbed  then  nothing  is  to  be  done.  On 
the  contrary,  if  it  persists  without  any  notable  modification,  inter- 
vention is  indicated.  If  the  fluid  is  allowed  to  remain  too  long, 
atrophy  of  the  lungs,  thickenings,  and  adhesions  may  occur,  which 
embarrass  the  function  of  the  organs  and  bring  about  deformity  of 
the  thorax.  Thoracentesis  is  practised  generally  toward  the  fifteenth 
day  in  children  and  the  twentieth  day  in  adults.  All  the  fluid  is  not 
drawn,  however;  at  most  one  quart  (one  litre)  should  be  evacuated. 
If  the  fluid  is  reproduced  a  new  puncture  may  be  made.  In  most 
cases,  however,  after  the  first  evacuation  absorption  is  completed  of 
itself.  This  fact  is  not  to  be  wondered  at.  It  is  the  application 
to  serous  membranes  of  the  general  law  of  pathology.  Every  mi- 
crobic  lesion  at  the  end  of  a  certain  time  no  longer  tends  to  arouse 
organic  reactions.  The  economy  becomes  accustomed  to  the  presence 
of  an  infectious  focus  which  at  first  arouses  its  susceptibility.  A 
modus  vivendi  which  may  be  prolonged  almost  indefinitely  is  thus 
established.  Intervention  is  then  indicated.  The  organism  being 
sluggish,  the  operation  renews  the  inflammatory  process  and  pro- 
duces an  increased  circulatory  activity  in  the  lungs,  and  the  change 
thus  caused  is  eminently  favorable  to  the  absorption  of  the  exudate. 
There  is  another  question  to  which  hardly  an  allusion  has  thus  far 
been  made.     Do  exudates  in  general  or,  what  is  easier  to  study, 


774  INFECTIOUS  DISEASES. 

pleural  effusions  contain  figurate  elements  or  soluble  substances 
exerting  any  action  whatever  upon  the  organism,  either  favorable 
or  otherwise?  At  present  it  is  well  known  that  even  serous  and 
transparent  effusions  alwa)rs  contain  leucocytes.  What  is  the  sig- 
mficance  of  then  presence  from  the  standpoint  of  the  protection  of 
the  organism?  Of  this  we  know  nothing,  and  we  do  not  comprehend 
their  role  in  those  cases  in  which  the  exudate  is  germless.  On  the 
other  hand,  as  has  already  been  stated,  even  a  serous  effusion  may 
contain  bacteria,  notably  streptococci.  In  the  case  of  tuberculosis, 
it  often  contains  the  specific  bacillus,  as  has  been  demonstrated  by 
inoculations  into  animals.  This  presence  of  microbes  in  certain 
exudates  might,  perhaps,  justify  and  command  earlier  intervention. 
The  author  says  "perhaps,"  because,  besides  the  difficulty  encoun- 
tered in  determining  whether  living  bacteria  are  present  in  an  exudate 
or  not,  it  may  furthermore  be  questioned  whether  these  bacteria  are 
really  noxious.  Immersed  as  they  are  in  a  great  amount  of  germi- 
cidal fluid,  they  seem  to  have  lost  all  pathogenic  action,  since  they 
are  incapable  of  inducing  even  a  purulent  transformation  of  the 
exudate.  Investigations  should  be  pursued  on  this  subject.  It  would 
also  be  interesting  to  take  up  the  study  of  soluble  toxic  or  antitoxic 
substances  which  may  be  present  in  an  exudate.  Dr.  Gilbert  (of 
Geneva)  laid  down  the  problem  by  showing  that  the  fluid  of  tuber- 
cular pleurisies,  when  injected  beneath  the  skin,  exerts  a  curative 
action.  It  is  true  that  the  fact  has  been  doubted.  The  author  has 
therefore,  with  Dr.  Josue,  pursued  some  researches  with  the  fluid  of 
experimental  diphtheritic  pleurisies.  The  results  were  negative,  inas- 
much as  the  fluid  experimentally  produced  in  guinea-pigs  contained 
neither  toxin  nor  antitoxin. 

We  have  expanded  upon  pleural  effusions,  for  they  are  the  most 
frequent,  while  exudates  in  other  serous  membranes  are  of  quite 
uncommon  occurrence.  While,  in  the  case  of  pleurisies  the  physician 
must  be  guided  in  his  intervention  by  the  physical  signs  and  the 
course  of  evolution,  and  not  by  the  functional  disturbances  which  are 
extremely  deceiving,  in  the  case  of  pericardial  or  meningeal  effu- 
sions he  must  act  altogether  differently.  In  the  case  of  the  peri- 
cardium the  physician  must  intervene  when  the  effusion  endangers 
the  function  of  the  heart,  and  in  the  case  of  the  meninges,  when 
the  exudate  produces  compression  and  intense  headache.  Lumbar 
puncture  relieves  the  pain  and  temporarily  reduces  the  increased 
intrameningeal   tension   as  well   as   certain   alarming  phenomena, 


THERAPEUTICS  OF  INFECTIOUS  DISEASE8.  775 

notably  coma.     In  most  cases  amelioration  i    tran  itorj  and  only 
delays  the  fatal  termination.     Neverthele    ,  there  are  certain  < 
on  record  in  which  repeated  punctures  seem  to  haVe  contributed  to 
recovery.    M  any  rate,  this  inoffem  ive  operation   eem    dei  tined  to 
be  retained  in  medical  practice  as  a  palliative. 

Acute  inflammations  of  the  peritoneum,  unlike  those  of  the  pleura, 
seldom  result  iii  aserous  effusion  which,  in  case  if  should  be  produced, 
is  too  small  in  amounl  to  necessitate  operal  ive  intervention.  In  fact, 
there  is  a  production  of  pseudomembranous  exudates  which  embar- 
rass intestinal  movements.  'This  is  a  fortunate  event,  since  the 
extension  of  the  peritoneal  inflammation  is  nothing  else  than  a  series 
of  inoculations  which  lake  place  from  point  to  point  ac  a  resull  of 
contractions  of  the  intestine.  It  is  well,  therefore,  to  complete  the 
work  of  nature  by  further  immobilizing  the  intestinal  coils,  a  resull 
that  may  be  obtained  by  the  administration  of  opium  or  morphine. 
Operative  intervention  is  at  times  indicated  only  in  subacute  or 
chronic  infections,  and  notably  in  tuberculosis.  Two  kinds  of  opera- 
tions may  be  performed:  one  simply  palliative,  the  other  curative. 
In  the  so-called  ascitic  form  of  tubercular  peritonitis  paracentesis  is 
practised  because  the  effusion,  owing  to  its  abundance,  produces 
functional  disorders.  The  liquid,  however,  is  seldom  sufficiently  pro- 
fuse to  render  this  operation  necessary,  and,  on  the  other  hand,  it  is 
generally  contained  between  adhesive  bands  of  pseudomembranes 
which  prevent  its  free  flow.  It  is  true  that  the  operation  may  be 
completed  by  irrigating  the  serous  membrane  by  means  of  boiled 
borated  water  at  102.2°  or  104°  F.  (39°  or  40°  C).  Irrigation  is 
continued  until  the  returning  fluid  becomes  perfectly  clear.  This 
method,  for  which  we  arc  indebted  to  Dr.  Debove.  has  been  employed 
with  success  in  a  number  of  cases.  The  irrigations  are  followed  by 
a  sufficiently  strong  inflammatory  reaction.  The  lesions  subse- 
quently undergo  resolution.  Another  procedure,  the  efficacy  of 
which  was  demonstrated  by  the  experiments  of  Dr.  Teissier,  col 
in  injecting  into  the  peritoneum  sterilized  gases — oxygen  or  nitrogen. 

Lastly,  one  of  the  most  extraordinary  therapeutic  methods  applied 
to  tubercular  peritonitis  is  laparotomy.  The  peritoneal  cavity  is 
opened,  and  then,  after  irrigation  by  means  of  boiled  water,  it  is 
dressed.  As  a  result  the  lesions  subside.  In  this  manner  recovery 
has  been  obtained  in  7.5  per  cent,  of  the  cases  in  adults  and  87  per 
cent,  in  children.  This  is  what  takes  place,  at  least  in  the  ascitic 
form.    In  the  ulcerative  variety,  out  of  twenty-two  laparotomies  nine 


776  1SFECTI0US  DISEASES. 

were  followed  by  death.  Out  of  thirteen  other  patients,  only  three 
remained  in  a  satisfactory  slate.  Finally,  in  the  fibrous  variety, 
recovery  reaches  65  per  cent.  The  mechanism  of  recovery  following 
operative  intervention  has  been  a  subject  of  extensive  discussion. 
Numerous  experiments  have  been  undertaken  bearing  upon  this 
subject.  All  clinical  as  well  as  experimental  documents  show  that 
laparotomy  succeeds  particularly  in  those  cases  which  tend  toward 
recovery  or  at  least  toward  a  chronic  state  compatible  with  life.  The 
slightest  cause  is  then  sufficient  to  arouse  the  sluggish  reactions  of 
the  organism.  Laparotomy,  still  better  than  aseptic  irrigations  or 
injections  of  gas,  produces  a  slight  inflammation  and,  necessitating 
an  effort  of  reparation  on  the  part  of  the  organism,  brings  about 
cicatrization  of  both  the  operative  wound  and  the  pre-existing 
lesions.  The  organism,  being  forced  to  supply  cells  and  to  secrete 
exudates  for  the  reparation  of  the  surgical  incision,  resumes  coinci- 
dent ly  the  work  which  it  had  once  begun  for  the  destruction  of  the 
tubercle  and  of  the  infectious  agents  living  therein.  In  brief,  all 
these  therapeutic  procedures  act  simply  by  awakening  a  curative 
inflammation  which  had  too  soon  fallen  into  slumber. 

Serous  effusions  of  the  tunica  vaginalis  or  of  the  articular  synovials 
seldom  invite  operative  intervention.  In  cases  in  which  the  pain 
caused  by  inflammation  of  the  tunica  vaginalis  is  very  intense,  a 
puncture  is  practised  which,  diminishing  the  tension,  causes  the 
painful  phenomena  to  disappear.  Finally,  as  in  the  case  of  the  pleura, 
when  the  effusions  pass  into  a  chronic  state  and  present  no  tendency 
to  absorption,  the  fluid  must  be  evacuated.  As  in  the  case  of  the 
pleura,  however,  it  seems  that  effusions  of  the  serous  membranes  are 
always  produced  consecutively  to  a  lesion  of  the  neighboring  parts, 
and  especially  of  subjacent  organs.  Hydrocele  is  a  true  chronic 
inflammation  of  the  tunica  vaginalis.  It  is  to  be  noted  that,  unlike 
what  occurs  in  other  serous  membranes,  evacuation  of  the  fluid  does 
not  suffice  to  bring  about  recovery.  It  is  necessary,  in  addition,  to 
inject  an  irritant  and  give  rise  to  a  curative  inflammation. 

In  those  cases  in  which  the  serous  exudates  raise  the  epidermis  or 
the  epithelial  lining  of  a  mucous  membrane  which  is  readily  accessible 
immediate  intervention  is  evidently  indicated.  The  bulla  should  be 
punctured  by  means  of  a  sterilized  needle,  and  the  fluid  evacuated 
by  gentle  pressure  with  the  finger.  The  operation  is  done  precisely 
as  in  the  dressing  after  the  application  of  a  vesicatory.  By  this 
small  operation  the  painful  tension  is  diminished  and  the  liquid 


THERAPEUTICS  OF  INFECTIOUS  DISEA8ES.  Ill 

containing  microbes  and  toxins  is  thrown  out.  Finally,  repair  us 
favored  because,  wiilioul  this  precaution,  suppuration  or  ulceration 
might  take  place. 

When  serous  exudates  are  produced  in  visceral  cavitie  and  oot- 
ably  in  the  digestive  bract,  an  easy  issue  is  assured.  The  organism 
daily  employs  this  means  of  defense.  Vomiting  and  diarrhea  repre- 
sent the  production  of  serous  secretions  designed  to  combat  infec- 
tion, viz.,  to  eliminate  microbes  and  their  toxins.  Therapeutii 
guided  by  the  same  principles  in  prescribing  emetict  and  purgati 
These  medicines  produce  secretions  which  wash  the  affected  parts. 
An  emetic  may  likewise  serve  to  eject  exudates  produced  in  the 
respiratory  apparatus.  The  movements  of  the  diaphragm  :md  the 
thoracic  muscles  compress  the  lungs  and  expel  the  pathological  fluids 
encumbering  (hem. 

Treatment  of  Purulent  Exudates.  While  serous  exudate-  are  dan- 
gerous only  by  their  quantity  and  the  disturbances  which  they 
mechanically  cause  in  the  neighboring  organs,  purulent  exudates  are 
of  greater  importance  and  require  more  prompt  intervention. 

Purulent  transformation  is  indicative  of  great  activity  on  the  pah 
of  the  pathogenic  agents.  Their  toxins  give  rise  to  profuse  diape- 
desis.  While  the  leucocytes  are  not  killed  in  the  yellow  serous  exu- 
date, in  pus  they  undergo  a  special  transformation — a  fermentation 
— which  causes  their  death  and  changes  them  into  useless  foreign 
bodies.  As  has  already  been  stated,  a  serous  effusion  produces  noth- 
ing more  than  mechanical  disturbances.  A  purulent  effusion,  on  the 
other  hand,  modifies  the  organism  more  profoundly.  The  general 
state  is  affected,  fever  sets  in,  and  grave  phenomena  may  appear. 
This  different  mode  of  action  of  the  two  kinds  of  effusions  results  in 
profound  difference  in  the  reactions  of  the  organism.  When  effusion 
is  of  a  serous  character,  the  organism  makes  no  effort  to  throw  it 
out;  when  effusion  is  purulent,  modifications  which  terminate  in  the 
evacuation  of  the  morbid  focus  occur.  This  is  the  tendency  of  every 
purulent  focus,  viz.,  to  open  outward  or  into  a  cavity.  These  spon- 
taneous openings,  however,  have  three  inconveniences:  they  may 
occur  in  an  organ  of  great  physiological  importance  or  enter  a  cavity 
which  may  serve  as  an  excellent  medium  for  the  multiplication  of 
the  microbe.  The  result  is  often  the  occurrence  of  serious  accidents 
rapidly  ending  in  death.  A  visceral  abscess,  until  then  well  borne. 
when  it  discharges  into  the  peritoneal  cavity,  produces  inflammation 
in  the  serous  membrane  which  ends  fatally.    In  this  case  the  organ- 


778  1XFECTI0  US  DISEASES. 

ism  follows  its  tendency  to  throw  out  the  harmful  element,  but  its 
intervention  is  blind  and  gives  rise  to  graver  disorders  than  the 
primary  lesion. 

The  second  inconvenience  of  spontaneous  openings,  even  of  those 
which  occur  under  favorable  conditions,  is  that  they  are  effected  too 
tardily.  The  consequence  is  that  the  organism  is  subjected  too  long 
to  the  action  of  toxins  and  that  the  adjoining  parts  of  the  purulent 
focus  are  too  profoundly  altered  to  recover.  Finally,  the  spontaneous 
openings  are  generally  too  small,  the  discharge  is  not  well  effected, 
and  the  pus  stagnates  and  may  undergo  putrid  decomposition.  Or 
else  fistulous  tracts  are  produced,  ending  in  the  formation  of  per- 
manent fistulae.  If  suppuration  is  finally  arrested,  deformed  cica- 
trices persist  which  often  cause  functional  difficulties.  These  con- 
siderations explain  why  timely  intervention  is  necessary.  Incision 
permits  the  flow  of  the  pus  under  the  most  favorable  conditions  at 
the  most  favorable  point,  through  a  sufficiently  large  opening  and 
at  a  period  when  the  economy  is  not  too  profoundly  intoxicated  and 
when  the  neighboring  parts  of  the  focus  are  not  yet  deeply  affected. 
Incision  must  be  practised  as  soon  as  the  pus  is  collected,  and  it 
must  be  made  at  a  low  point.  If  the  focus  is  large  and  presents 
ventricles,  it  is  often  necessary  to  make  count eropenings.  In  order 
to  assure  the  flow  of  the  fluid  and  prevent  the  incision  from  closing 
prematurely,  the  lips  of  the  wound  should  be  kept  open  by  means 
of  gauze  or  drainage-tubes.  When  dealing  with  a  voluminous  but 
well-circumscribed  abscess,  situated  in  the  face  or  neck,  the  author 
has  been  in  the  habit  of  making  a  small  puncture  and  introducing 
into  the  focus  Florence  horsehair  curved  in  arch-shape  in  order  to 
avoid  a  cicatrix.  In  this  way  a  very  easy  discharge  is  assured,  and 
the  incision  is  so  small  as,  in  most  cases,  to  leave  no  visible  mark. 

In  all  cases  the  discharge  should  continue  for  a  few  days  following 
the  incision.  The  exudate  then  represents  a  sort  of  washing  per- 
formed by  the  organism  for  eliminating  the  microbes  and  toxins. 
Guided  by  this  fact,  lavage  with  aseptic  or  slightly  antiseptic  fluids 
may  be  employed,  and  the  work  of  nature  thus  be  completed.  These 
lavages  also  have  the  advantage  of  detaching  and  washing  out  dead 
cells,  small  foreign  bodies,  and  at  times  sequestrse.  Spontaneous 
rejection  of  these  harmful  elements  is  long  and  difficult.  Even  lavage 
may  be  insufficient  to  carry  them  away.  Then  curettage  and,  in 
certain  cases,  more  important  operations  are  resorted  to  for  the 
purpose  of  exposing  necrosed  parts  and  extracting  them.    An  osseous 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  ~",'.i 

sequestrum,  for  example,  may  keep  up  8  discharge  for  years,  but 
when  it  is  extirpated,  recovery  follow  in  a  i<-v.  d&] 

Medical  advance,  by  enabling  the  practitioner  to  detect  visceral 
suppurations  and  establish  their  localization  by  the  study  of  symp- 
toms, have  led  him  to  intervene  in  ca  e  of  deep  eated  lesions, 
visceral  abscesses,  such  as  those  of  the  liver,  kidneys,  and  lung  .  or 
of  the  nervous  centres,  and  t<>  open  serou  cavities,  and  to  trepan  ;i 
bone.  Surgical  intervention  is  not,  however,  always  indi  pensable. 
Purulent  foci  are  sometimes  suppressed  spontaneously,  and  the 
microbes  perish.  The  pus  is  then  absorbed  or  undergoes  fatty  meta- 
morphoses, or  else  it  is  transformed  into  a  semisolid  mass  which  may 
later  become  iu(illr;ited  with  calcareous  salts,  and  thus  be  rendered 
entirely  inoffensive.  In  order  to  formulate  the  rules  of  intervention, 
we  must  take  into  aceounl  ;i  good  many  factors,  such  as  the  seat  of 
the  lesion,  the  nature  of  the  causative  microbe,  the  course  of  the  local 
symptoms,  and  the  concomitant  general  phenomena.  As  regards 
localization,  it  will  suffice  to  recall  what  occurs  in  the  serous  cavities. 
Intervention  must  be  immediate  in  the  case;  of  the  peritoneum,  in 
order  to  prevent  an  early  fatal  termination,  and  it  must  be  prompt 
in  the  case  of  articulations,  in  order  to  prevent  consecutive  ankyl<  «is. 
On  the  other  hand,  purulent  pleurisy  is  far  better  borne,  and  at 
times,  when  it  is  encysted,  it  may  heal  spontaneously  by  vomica. 
Early  intervention  is,  however,  preferable,  since  it  prevents  second- 
ary alterations  of  the  lungs  and  pleura.  The  nature  of  the  causative 
agent  is  also  to  be  considered.  .As  a  rule,  suppurations  with  strep- 
tococci require  rapid  intervention  and  radical  operation.  A  large 
incision,  assuring  an  easy  flow,  is  indispensable.  Suppurations  due 
to  pneumococci  are  less  liable  to  be  reproduced  and  often  recover  in 
consequence  of  simple  evacuative  puncture.  Finally,  non-microbic 
suppurations  are  commonly  well  borne  and  may  be  absorbed  with- 
out operative  intervention. 

Besides  bacteriological  examination,  which  alone  can  conclusively 
demonstrate  the  nature  of  the  causative  agent,  therapeutic  indica- 
tions may  be  drawn  from  the  local  and  general  phenomena.  Thus 
the  author  lias  seen  the  development  of  a  pleuritic  effusion  during 
convalescence  from  typhoid  fever.  This  effusion,  occurring  without 
any  functional  disturbance  and  giving  rise  to  no  fever,  seemed  to  be 
of  a  serous  nature.  In  order  to  assure  the  diagnosis,  however,  a  few 
days  later  the  author  made  an  exploratory  puncture,  which  brought 
out  a  seropurulent  liquid.  The  latter,  however,  contained  no  microbe. 


780  INFECTIOUS  DISEASES. 

but  agglutinated  energetically  the  typhoid  bacillus.  As  the  general 
state  seemed  to  be  very  satisfactory,  he  did  no  more  than  apply  a 
few  cutaneous  revulsives,  and  the  fluid  was  gradually  absorbed  and 
disappeared.  Here  is  a  case  in  which  the  study  of  the  morbid  symp- 
toms did  not  justify  intervention;  but  in  the  case  of  an  erroneous 
interpretation  of  the  nature  of  the  effusion,  exploratory  puncture, 
by  giving  exact  information,  might  have  modified  our  first  conclu- 
sion. Bacteriological  examination,  however,  brought  us  back  to  the 
idea  of  abstention,  and  the  evolution  demonstrated  that  hi  fact  it 
was  useless  to  intervene. 

We  cannot  review  all  the  indications  and  contraindications  that 
are  to  be  taken  into  account  when  the  rules  of  intervention  are  to 
be  settled.  While  in  certain  cases  these  rules  are  relatively  simple, 
in  others  discussion  is  not  yet  at  an  end.  It  will  suffice  to  recall  what 
occurs  as  regards  appendicitis.  The  lesion  is  not  treated  by  incision 
of  the  focus,  but  by  extirpation  of  the  diseased  organ.  While  certain 
surgeons  operate  as  soon  as  the  diagnosis  is  made,  others  prefer  to 
wait  and  not  intervene  until  after  the  disappearance  of  the  acute 
symptoms.  In  view  of  the  discussions  that  have  taken  place  and  of 
the  contradictory  facts  that  have  been  reported,  it  may  be  stated 
that  at  the  present  time  no  problem  is  more  troublesome,  no  question 
engages  more  responsibility  or  produces  more  anxiety  than  the  advice 
to  be  given  in  cases  of  appendicitis. 

Although  surgical  intervention  is  possible  when  suppuration  is 
localized  at  a  point,  it  cannot  evidently  be  resorted  to  against  small 
disseminated  lesions.  We  may  open  a  pulmonary  abscess,  but  we 
are  unable  to  intervene  against  a  purulent  bronchitis  or  a  broncho- 
pneumonia which  has  terminated  in  multiple  lobular  suppurations. 
In  this  case  the  organism  endeavors  to  eject  the  purulent  exudates 
by  coughing  and  at  times  by  vomiting.  The  physician  must  act  in 
the  same  manner.  He  must  prescribe  substances  which  favor  lique- 
faction of  the  exudate  and,  consecutively,  its  ejection  through 
expectoration.  The  sulphur  and  antimony  preparations  are  indi- 
cated here.  If  this  medication  proves  insufficient,  an  emetic  may 
accomplish  more  thorough  cleansing  of  the  respiratory  apparatus. 
While,  however,  an  emetic  yields  good  results  in  young  children,  the 
older  the  patient  the  less  easily  he  can  bear  it.  It  should  never  be 
employed  in  the  aged,  since  it  may,  by  the  efforts  which  it  produces, 
cause  vascular  ruptures  or,  at  least,  give  rise  to  considerable  depres- 
sion and  collapse. 


THEBAPEUTI08  OF  INFECTIOUS  DISEASES.  781 

Treatment  of  Pseudomembranous  Exudates.  The  third  vai 
of  inflammatory  exudates  is  represented  by  pi  eudomembrai 
dates.  The  therapeutic  rule  i:p  here  very  simple.  The  fal  e  mem- 
brane is  a  barrier  opposed  to  the  infection,  l»ui  il  i-  bill  of  microb<  ■ 
and  toxins.  The  organism  should,  therefore,  be  freed  from  it.  Tib- 
may  be  accomplished  by  irrigations,  scrapings,  forcible  removal  of 
the  membrane,  and  cleansing  by  means  of  forcep  01  cotton.  The 
only  precaution  to  be  I  a  ken  is  to  avoid  as  much  a  po  rible  hurting 
the  subjaeenl  niucous  nienibrane.  Ii  is  precisely  for  this  reason  thai 
many  advocate  abstention,  al  least  in  cases  of  angina,  since  too 
energetic  intervention  might  harm  the  mucous  membrane.  They 
endeavor  to  detach  (he  pseudomembranous  exudates  by  means  of 
irrigations.     Al  any  rale,  intervention  is  far  leSfi  Ulgenl  than  in  cases 

of  suppuration,  for  tlie  pseudomembrane  represents  a  barrier  oppos- 
ing the  progress  of  the  infection.   As  we  have  several  times  remarked, 

while  warding  off  certain  dangers  the  pseudomembrane  may  create 
others.  By  reason  of  its  localization  it  may  bring  about  serious 
functional  disturbances  and  necessitate  surgical  intervention,  such 
as  tracheotomy,  which  is  rather  a  palliative. 

Treatment  of  Gangrenous  Lesions.  The  more  noxious  the  inflam- 
matory exudates  the  more  prompt  and  energetic  intervention  must 
be.  In  the  case  of  a  gangrenous  or  putrid  lesion,  operation  must  be 
performed  as  soon  as  possible,  for  the  reason  that  the  toxins  produced 
by  the  microbes  are  so  strong  that  the  cells  in  contact  with  them 
cannot  react,  but  die  and  undergo  putrefaction,  which  adds  new 
harmful  substances  to  the  medium.  These  putrid  poisons  being 
absorbed,  impregnate  the  entire  economy  and  rapidly  produce  a  very 
grave  general  condition. 

As  soon  as  the  existence  of  a  putrid  or  gangrenous  focus  is  deter- 
mined, it  must  be  freely  incised  and,  if  possible,  the  walls  must  be 
scraped  and  frequent  irrigations  practised.  These  rules  are  easily 
applicable  to  putrid  pleurisies.  They  may  also  be  employed  Lac 
of  pulmonary  gangrene.  Unfortunately,  in  the  latter  case  interven- 
tion is  more  uncertain,  and  the  individuals  operated  upon  too  often 
succumb,  at  times  tardily,  to  uncontrollable  hemorrhages. 

For  the  treatment  of  gangrenes  the  author  has  for  some  time  been 
in  the  habit  of  employing  peroxide  of  hydrogen.  Many  patients  suf- 
fering from  erysipelas  or  a  gangrenous  phlegmon  of  the  extremities 
recovered  under  this  procedure.  The  author  prescribes  every  day  a 
local  bath,  lasting  for  an  hour,  in  a  1: 10.000  solution  oi  potassium 


782  INFECTIOUS  DISEASES. 

permanganate.  The  limb  is  then  surrounded  with  compresses  of 
peroxide  of  hydrogen.  In  mild  cases  this  treatment  is  sufficient.  In 
grave  cases  a  subcutaneous  or  interstitial  injection  of  peroxide  of 
hydrogen  is  given  morning  and  evening.  The  author  employs  the 
commercial  solution,  to  which  is  added  an  equal  volume  of  a  4: 1000 
sodium  bicarbonate  solution.  Morning  and  evening  5  c.cm.  or  6  c.cni. 
sometimes  10  c.cm.  of  this  solution,  are  injected  through  several  punc- 
tures all  around  the  sphacelated  parts.  The  injections  are  given  very 
slowly,  so  as  not  to  distend  the  tissues  too  rapidly  by  the  gas  and  to 
avoid  penetration  into  some  open  bloodvessel.  Under  this  treat- 
ment putrefaction  is  arrested  and  the  eschars  are  soon  detached. 

When  a  gangrenous  focus  is  limited  the  resistance  of  the  organism 
is  not  yet  overcome,  and  consequently  operative  assistance  may  be 
of  service.  If,  however,  the  lesion  is  diffuse,  if  the  tissues  are  simply 
the  seat  of  a  sphacelus  in  the  absence  of  a  focus,  the  diseased  parts 
cannot  be  extirpated.  Such  is  notably  the  case  in  gangrene  of  the 
extremities.  When  the  lesions  are  extensive  but  superficial,  for 
instance,  as  a  result  of  lymphangitis  and  erysipelas  of  the  lower 
extremities,  if  the  general  state  is  fairly  satisfactory,  recovery  may 
be  obtained  by  means  of  appropriate  dressings,  by  the  employment 
of  antiseptics  and  subcutaneous  injections  of  peroxide  of  hydrogen. 
Too  often,  however,  the  toxins  produced  in  the  necrosed  parts  give 
rise  to  serious  symptoms  and  necessitate  amputation  of  the  extremity 
above  the  diseased  parts.  This  operation  is  the  only  one  available  in 
cases  of  total  or  diffuse  gangrene.  Whether  the  accidents  are  due 
to  an  acute  or  chronic  arteritis  or  are  dependent  upon  the  septic 
vibrio,  there  is  no  chance  of  recovery  except  by  removing  the  entire 
diseased  parts.  In  some  cases,  however,  the  apparently  healthy 
tissues  are  already  invaded  and  the  gangrenous  process  reappears  in 
the  operative  wound. 

Gangrenes  are  not  always  hopeless  as  regards  prognosis.  An  affec- 
tion designated  by  the  characteristic  name  benign  gangrene  of  the 
bronchial  extremities  has  long  been  known.  We  have  reported 
observations  of  gangrenous  mammitis  and  of  curable  gangrene  of  the 
eyelids  which  have  terminated  without  causing  any  serious  symp- 
toms. Lastly,  among  gangrenous  anginas  there  are  some  in  which 
the  limited  sphacelus  only  slightly  disturbs  the  general  condition  of 
the  patient.  In  all  these  cases  the  indication  is  the  same  as  for 
purulent  exudates,  and  local  intervention  or  antiseptics  render  the 
greater  service. 


THEBAPEUTICB  OF  INFECTIOUS  DISEASES. 

Treatment  of  Nodular  Lesions.  The  lael  form  of  inflammatory 
reaction  consists  in  the  production  of  nodules  the  extenl  ol  which  i- 
extremely  variable.  When  small,  the  granulations  are  generally  very 
numerous  and  disseminated,  and  intervention  is  impo  ible.  When 
they  are  united  in  a  mass  they  behave  as  a  tumor  and  require  the 
same  fcreatmenl  as  the  latter  thai  is,  extirpation.  Finally,  when 
the  mass,  after  having  been  caseated,  is  softened,  treatment  is  the 
same  as  in  cases  of  suppurating  foci,  [n  both  orders  of  lesions  'I  e 
natural  tendency  is  to  open  outwardly,  bul  the  opening  i  tardy  and 
insufficient.  We  must,  therefore,  intervene,  incise  the  focus,  scrape 
the  walls,  extirpate  the  parts  too  profoundly  altered,  and  then  keep 
in  contact  with  the  locus  modifying  substances  or  antiseptics.  Among 
the  latter  iodine  preparations  are  most  commonly  employed. 

It  is  not  to  be  overlooked,  however,  thai  in  tuberculosis  surgical 
intervention  has  sometimes  been  the  point  of  departure  for  an  acute 
attack. 

Patients  who  supported  a  local  lesion  fairly  well  have,  in  conse- 
quence of  an  operation,  developed  grave  symptoms  and  succumbed 
to  an  attack  of  acute  miliary  tuberculosis. 

Treatment  of  Hemorrhages.  Hemorrhages  occurring  in  the 
course  of  infectious  diseases  may  be  divided  into  two  groups:  Some 
are  local  hemorrhages  produced  in  an  inflamed  part  as  a  result  of  the 
too  great  intensity  of  morbid  phenomena  and  the  accidental  altera- 
tion of  bloodvessels.  Hemorrhage  may  be  slight  or  grave.  I  ransitory 
or  recurring,  but  it  is  generally  produced  at  one  point  or  at  a  series 
of  points  close  to  each  other.  The  second  group  comprises  hemor- 
rhages resulting  from  general  modification  of  the  organism.  These 
are  not  necessarily  serious.  In  a  good  many  infections,  small  cuta- 
neous hemorrhages  occur  which  in  nowise  render  prognosis  unfavor- 
able. Such  is  not  the  case,  however,  when  multiple  and  repeated 
hemorrhages  take  place.  We  are  then  in  the  presence  of  the  hemor- 
rhagic forms  of  infections.  To  this  group  belong  the  putrid  fevers 
of  the  ancients.  In  this  case  the  treatment  must  be  directed  to 
modify  the  general  state  of  the  economy,  and  particularly  the 
chemical  constitution  of  the  blood. 

Hemorrhages  Due  to  Local  Causes.  Hemorrhages  arising  from  local 
causes  may  be  due  to  particularly  intense  inflammation.  Conges- 
tion in  this  case  terminates  in  rupture.  In  other  instances  inflam- 
mation is  mild,  but  occurs  in  an  individual  predisposed  To  local  or 
general   hemorrhages.     Lastly,  in    a    third  group  may  be    classed 


784  INFECTIOUS  DISEASES. 

those  cases  in  which  a  morbid  process  involves  a  bloodvessel  and 
ulcerates  it. 

Hemorrhages  resulting;  from  too  great  intensity  of  a  reactionary 
process  are  frequent  and,  as  a  rule,  of  little  gravity.  They  may  be 
observed  in  the  skin,  in  the  mucous  membranes,  and  in  the  organs. 
Infectious  exanthemata  and  enanthemata,  when  somewhat  intense, 
produce  small  vascular  ruptures,  especially  in  those  parts  in  which 
the  circulation  is  more  or  less  embarrassed.  When  scarlatinal  erup- 
tion is  intense  small  patches  of  purpura,  which  have  no  prognostic 
value,  are  often  observed,  particularly  in  the  lower  extremities.  Simi- 
larly, in  cases  of  confluent  variola,  the  pustules  upon  the  legs  and 
hands  are  sometimes  filled  with  blood;  their  color  changes;  they 
become  brownish,  and  are  soon  covered  with  black  crusts.  These 
small  hemorrhages  have  no  serious  significance.  They  often  seem  to 
exercise  even  a  favorable  action  upon  the  course  of  the  local  process. 

Small  hemorrhages  are  likewise  produced  in  inflamed  mucous  mem- 
branes. At  times  they  present  a  spotted  aspect.  For  example,  a 
mottled  red  patch  occurs  in  the  throat  in  cases  of  angina,  In  some 
cases,  as  the  mucous  membrane  is  less  resistant  than  the  skin,  the 
blood  flows  out.  In  the  case  of  coryza,  epistaxis  is  the  result;  in  the 
case  of  angina,  laryngitis  and  bronchitis,  some  spitting  of  blood;  in 
cases  of  gastritis  or  intense  enteritis  blood  appears  in  the  vomit  and 
dejecta.  The  intestinal  hemorrhages  occurring  at  the  beginning  of 
typhoid  fever  must  likewise  be  attributed  to  the  great  violence  of 
the  infectious  process.  As  is  known,  their  prognosis  is  generally 
favorable.  Among  the  hemorrhages  which  may  take  place  in  paren- 
chymatous organs,  those  interesting  for  the  therapeutist  are  ex- 
pressed by  appreciable  symptoms.  In  this  connection  two  organs 
particularly  deserve  study:  the  lungs  and  the  kidneys. 

In  cases  of  bronchopneumonia  infarctions  may  occur  in  the  in- 
flamed nodules,  but  they  generally  remain  unnoticed.  More  exten- 
sive infarctions  give  rise  to  bloody  expectoration.  In  the  kidneys, 
inflammatory  hemorrhages  are  frequent  and  readily  recognized  by 
hematuria.  In  primary  acute  and  in  scarlatinal  nephrites,  hematuria 
is  often  very  pronounced  and  sometimes  represents  the  first  morbid 
manifestation.  It  may  occur,  although  seldom,  in  erysipelas.  In 
this  instance,  however,  it  lasts  longer  than  in  scarlatinal  nephritis 
without  having  any  prognostic  gravity.  Hemorrhagic  nephritis  is 
altogether  rare  in  other  infections,  except  those  attended  by  multiple 
hemorrhages  indicating  profound  alteration  of  the  organism. 


THEBAPEUTI08  OF  INFECTIOUS  DISEASES.  785 

Now,  a  few  words  in  reference  to  hemorrhaged  dependent  upon 
individual  predisposition.  Small  eechymo  e  in  the  lower  extremities 
in  I  he  course  of  virions  erupl  i\  e  feven  ,  tnea  le  .  carlatina,  or  variola 
occur  in  subjects  having  voluminous  varices.  The  eruption  of 
me;isles  may  also  sometimes,  here  and  there,  assume  an  ecchymotic 
aspect.  This  occurs  particularly  in  children  suffering  from  whooping- 
cough  and  in  men  I aking  copaiba  (page  134).  [n other  instances  the 
hemorrhagic  tendency  is  explained  by  the  state  of  the  subject,  who 
is  suffering  from  a  previous  hemophilia,  or  who  is  under  the  influence 
of  another  infection  or  intoxication. 

Hemorrhages  resulting  from  the  extension  of  an  infect  ion-  pri 
into  bloodvessels  are  more  important.  In  most  cases  this  extension 
is  effected  so  slowly  as  to  permit  the  formation  of  a  vascular  throm- 
bosis. If,  however,  the  course  is  rapid  or  particularly  intense,  tie 
vessel  is  opened,  and  the  hemorrhage  thus  occurring  may  be  serious 
enough  to  cause  death,  as  it  may,  for  example,  happen  in  the  third 
stage  of  typhoid  fever. 

Hemorrhages  Due  to  General  Causes.      Along  with  hemorrhages  mi-- 

ing  from  local  causes  are  to  be  placed  those  dependent  upon  a  general 

modification  of  the  organism.  We  shall  divide  them  into  three 
groups.  A  hemorrhage  may  represent  a  symptom  of  infection .  Sue)  i 
is  the  case  in  purpura.  It  may  depend  upon  the  lesion  of  an  organ 
which  plays  an  important  role  in  the  coagulal  >ility  <  >f  the  blood.  Such 
is  the  case  in  infectious  grave  icterus.  Finally,  and  this  is  the  group 
which  we  must  particularly  study,  it  may  result  from  special  viru- 
lence of  the  pathogenic  germ.  They  then  constitute  a  particular 
form  of  the  disease  which,  in  certain  cases,  differs  entirely  from  the 
classical  type.  Thus,  hemorrhagic  forms  of  measles,  scarlatina,  and 
typhoid  fever  have  been  described.  These  facts  are,  however,  excep- 
tional, and  the  most  interesting  disease  from  this  standpoint  is 
undoubtedly  variola.  In  hemorrhagic  variola  bloody  effusions  may 
occur  in  any  tissue  and  organ.  There  may  be  observed  purpura, 
cutaneous  ecchymoses,  and  bullae,  subconjunctival  and  buccopharyn- 
geal ecchymoses,  epistaxis;  gastric,  intestinal,  uterine,  renal,  or  pul- 
monary hemorrhages,  and  extensive  bloody  infiltrations  beneath  the 
skin  and  in  the  serous  membranes.  However  multiple  they  may 
be,  however  many  parts  of  the  body  they  may  affect,  and  however 
grave  in  character,  hemorrhages  do  not  occur  at  all  points  of  the 
organism.  The  alteration  of  the  blood  does  not.  therefore,  explain 
the  phenomena  completely.    We  must  admit  either  a  predisposition 

50 


786  INFECTIOUS  DISEASES. 

or  some  concomitant  lesion  in  the  parts  which  become  the  seat  of 
the  bloody  effusion. 

Although  hemorrhagic  infections  mostly  belong  to  the  group  of 
general  in  lections,  a  localized  focus  may  give  rise  to  toxins  sufficiently 
abundant  and  active  to  impregnate  the  entire  economy  and  cause 
hemorrhages  at  points  distant  from  the  primary  lesion.  Dr.Dieulafoy 
has  called  attention  to  facts  of  this  kind  by  showing  that,  in  certain 
lesions  of  the  intestine,  and  notably  in  appendicitis,  noxious  sub- 
stances are  elaborated  which  explain  the  occurrence  of  hemorrhages 
at  distant  points — for  example,  hematemesis. 

The  preliminary  considerations  above  presented  show  us  how 
infectious  hemorrhages  maj7  be  divided  theoretically.  They  establish 
at  the  same  time  that,  in  the  majority  of  cases,  the  process  is  complex. 
The  therapeutist  must,  therefore,  frequently  resort  to  local  medica- 
tion as  well  as  to  medication  capable  of  modifying  the  general 
state. 

Therapeutic  Indications.  The  first  indication  is  to  prescribe  rest  and 
immobility.  A  movement  may  cause  detachment  of  the  clots  occlud- 
ing the  open  vessels,  and  thus  renew  the  hemorrhage.  In  the  case 
of  a  patient  for  whom  baths  have  been  prescribed,  these  should  be 
discontinued.  If  the  patient  is  agitated  or  delirious,  it  will  be  advis- 
able to  prescribe  soothing  medications,  for  instance,  opium  or  mor- 
phine, so  as  to  insure  complete  quiet.  Opium  is  generally  indicated 
when  the  patient  coughs,  even  though  no  bronchial  or  pulmonary 
hemorrhages  exist,  for  the  effort  involved  in  coughing  may  detach 
the  clot.  It  should  be  remembered  that  whooping-cough  is  of  itself 
sufficient  to  produce  hemorrhages.  These  precautions  being  taken, 
it  would  be  well  to  further  prescribe  substances  which  increase  the 
coagulability  of  the  blood.  Even  when  the  question  is  one  of  local 
hemorrhages,  the  dyscrasic  modifications  resulting  from  infection 
tend  to  maintain  or  aggravate  the  flow  of  blood.  For  this  purpose 
acid  beverages  have  long  been  in  use.  Citric  acid  or  sulphuric  acid 
lemonade  may  be  prescribed.  Haller  employed  in  hemorrhagic 
variola  the  acid  elixir  bearing  his  name  and  which  is  nothing  else 
than  a  dilution  of  sulphuric  acid.  Sydenham  asserted  that  sulphuric 
acid,  given  in  small  beer,  was  the  specific  medicine  for  confluent  and 
hemorrhagic  variola.  At  present  use  is  made  only  of  RabePs  water 
(Eau  de  Rabel)  which,  as  is  known,  is  a  mixture  of  100  parts  of 
official  sulphuric  acid,  300  parts  of  alcohol  (at  90°  F.),  and  4  parts 
of  petals  of  red  poppy.    Thus  is  formed  an  ethyl  sulphate  the  taste 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  787 

of  which  recalls  that  of  old  brandies.   One  may  prescribe  a  lemonade 

containing  f>  per  looo  of  Rabel's  water.     However,  the  author's 
experience  with  this  medication  in  cases  of  hemorrhagic  variola  ha 
not  boon  encouraging. 

At  present  we  possess  two  medicine  which  seem  capable  ol 
increasing  the  coagulability  of  the  blood:  one  of  them  i-  calcium 
chloride.  The  author  has  frequently  employed  thi  sail  in  the  treat- 
ment of  hemorrhagic  infections  and  notably  in  hemorrhagic  variola. 
In  two  or  three  days  hematurias  are  arrested,  as  well  as  enterorrha- 
gias  and  metrorrhagias.  In  spile  of  these  ameliorations,  however, 
many  patients  die.  As  ;i  few  pal ienls  suffering  from  pustular  variola 
with  hemorrhages  recovered,  and  as  the  medication  is  inoffensive,  the 
author  thinks  that  it  is  advisable  lo  resort  lo  it  in  all  such  C 
It  seems  to  bo  applicable  even  to  all  diseases  in  which  hemorrl 
are  due  to  defective  coagulability  of  the  blood.  Chloride  of  calcium 
thus  seems  destined  to  occupy  a  permanent  place  in  general  hemo- 
static medicines.  It  is  therefore  necessary  to  first  determine  its 
posology.  This  salt  is  not  very  toxic;  injected  into  the  veins  of  a 
rabbit  it  proves  fatal  when  100  c.cm.  of  a  1  per  cent,  solution,  that 
is,  1  gram  of  the  medicine  per  kilogram  of  animal  is  introduced. 
This  salt,  however,  is  caustic:  beneath  the  skin  it  produces  necrosis 
and  slough.  The  hypodermic  method  cannot,  therefore,  be  utilized. 
It  must  be  introduced  by  the  digestive  tract.  Either  the  anhydrous 
or  the  crystallized  chloride  may  be  prescribed  indifferently.  It 
should  be  remembered,  however,  that  the  former  is  twice  as  strong 
as  the  latter,  which,  as  is  known,  contains  six  molecules  of  water  of 
crystallization.  The  doses  above  indicated  are  those  of  the  crystal- 
lized chloride  of  calcium.  These  doses  should  be  reduced  one-half  if 
the  anhydrous  chloride  is  prescribed.  When  dissolved  in  water  or 
in  a  julep,  this  salt  has  a  very  disagreeable  flavor,  recalling  that  of 
sea  water,  leaving  in  the  mouth  a  metallic  taste.  It  is.  therefore, 
well  to  prescribe  it  in  some  excipient  which  will  mask  its  bast 
Rabuteau  prescribed  5  grams  of  calcium  chloride  in  400  grams  of 
simple  syrup  and  100  grams  of  peppermint-water.  The  daily  dose 
of  4  grams  (5j)>  which  is  at  times  prescribed,  seemed  to  him  by  far 
too  strong,  and  he  advised  the  administration  of  from  20  eg.  to  1  gram 
a  day  (3  to  15  grains). 

When  hemorrhages  must  be  arrested  these  doses  are  insufficient. 
The}r  may  be  considerably  increased  without  inconvenience.  The 
author  has  begun  with  giving  4  grams  (5j)-    Later,  when  treating  a 


788  INFECTIOUS  DISEASES. 

non-vaccinated  child, one  year  old, he  administered  from  1  to  11  grams 
(15  to  22  grains) ;  the  child  recovered.  The  author  then  thought  that 
the  doses  might  be  increased  for  adults,  and  he  cautiously  gave  as 
much  as  12  grams  ( o ii J )  m  twenty-four  hours.  This  result  demon- 
strates the  harmlessness  of  the  medicine  which,  contrary  to  the  opini<  n 
advanced  by  some  authorities,  exercises  no  purgative  action  even 
when  given  in  large  doses.  At  any  rate,  the  author  has  come  to 
recognize  that  it  is  useless  to  prescribe  such  considerable  quantities; 
4  grams  (oj)  a  day  suffice.  The  best  method  of  administering  the 
medicine  is  to  dissolve  it  in  a  potion  containing  syrup  of  bitter  orange- 
peel  and  including,  like  the  potion  of  Todd  of  the  Codex,  rum  and 
tincture  of  cinnamon. 

The  following  may  be  prescribed: 

Crystallized  calcium  chloride 4  to  6  grams  (3j-jss) 

Syrup  of  bitter  orange-peel  40  "       (5.i) 

Old  brandy  or  rum 30  "       (gj) 

Tincture  of  cinnamon 5  "        (5j) 

Distilled  water 50  "       (gij) 

This  potion  is  by  no  means  disagreeable.  It  may  readily  be  modi- 
fied by  increasing  the  quantity  of  rum  and,  if  the  taste  is  unpleasant, 
by  omitting  the  tincture  of  cinnamon.  A  potion  without  alcohol 
must  be  prescribed  when  a  renal  lesion  is  suspected.  The  syrup  of 
bitter  orange-peel  suffices  to  mask  the  taste,  but  not  as  completely 
as  in  the  formula  above  given.  Chloride  of  calcium  has  a  by  no 
means  less  important  employment  in  the  treatment  of  hemorrhagic 
nephrites.  In  cases  of  primary  or  secondary,  and  notably  of  scarla- 
tinal nephrites,  a  potion  containing  from  3  to  4  grams  of  calcium 
chloride  rapidly  diminishes  hematuria.  In  most  cases  the  urine 
contains  no  blood  at  the  end  of  two  or  three  days.  In  several  cases 
the  author  noticed  the  reappearance  of  hematuria  when  the  medicine 
was  discontinued.  As,  however,  it  is  admitted  that  the  salts  of 
calcium  diminish  the  coagulability  of  the  blood  at  the  end  of  a  few 
days,  instead  of  increasing  it,  the  author  has  constantly  suspended 
its  use  after  four  or  five  days.  If  necessary,  it  may  again  be  pre- 
scribed after  an  interruption  of  three  or  four  days. 

Since  the  contributions  of  Dastre  and  P.  Carnot,  gelatin  also  is 
known  to  have  the  property  of  increasing  the  coagulability  of  the 
blood.  Experiments  upon  animals  have  demonstrated  this.  The 
method  consists  in  injecting  the  substance  into  the  veins.  One  hesi- 
tates to  apply  the  method  in  man.    The  subcutaneous  channel  has, 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  thU 

therefore,  been  employed.  Physiologists  contend,  however,  that 
under  these  conditions  the  coagulability  of  the  blood  i  oo1  modified 
for  the  reason  that  the  substance  U  no1  absorbed.  The  author  hat 
tried  subcutaneous  injed  ion  of  gelal  in  in  i -\  era!  ca  e  of  hemorrhagic 
variola.  In  one  of  the  cases  the  results  were  excellent,  since  the 
symptoms  improved  and  thepatienl  recovered.  The  injected  liquid, 
however,  became  the  starting  poinl  of  a  gangrenous  phlegmon  which 
raised  the  entire  skin  of  the  abdomen  and  healed  only  after  a  con- 
siderable period  of  lime.  This  suppuration  i-  explained  by  the 
infected  condition  of  the  skin  in  variola.  It  is  interesting  to  note 
that  the  liquid  which  was  discharged  by  an  incision  contained  a 
great  amount  of  unaltered  gelatin. 

Satisfactory  results  may  he  obtained  when  the  chemical  modifi- 
cations of  the  blood  in  hemorrhagic  infections  are  discovered.  Now 
that  coagulating  ferments  and  fibrinogenous  substances  are  easily 
prepared,  it  might  be  possible  to  combat  a  hemorrhagic  tendency  by 
means  of  organic  extracts.  In  this  connection  the  condition  of  the 
liver  should,  perhaps,  receive  more  attention  than  has  hitherto  been 
given  to  it.  At  the  necropsy  of  individuals  succumbing  to  hemor- 
rhagic variola  the  author  has  always  detected  far  more  profound 
and  extensive  hepatic  lesions  than  in  cases  of  confluent  variola.  It 
may,  therefore,  be  questioned  whether  it  would  not  be  useful  to 
struggle  against  the  hepatic  insufficiency  by  means  of  opotherapy. 

Hemorrhages  may  be  combated  by  producing  vasoconstriction. 
This  is  obtained  indirectly  by  revulsion,  cuppings,  sinapisms,  and 
cold  beverages.  Vasoconstriction  may  also  be  effected  by  certain 
medicines,  chief  of  which  is  ergot.  The  hemostatic  action  of  ergot, 
which  is  doubted  03^  so  many,  seems  to  me  incontestable.  It  is  not, 
as  has  been  asserted  by  some,  the  muscular  fibres  of  the  uterus  alone 
that  are  influenced  by  it.  Nevertheless,  ergot  seems  to  the  author 
contraindicated  in  fevers  characterized  by  a  gangrenous  tendency 
in  which  the  nutrition  of  certain  parts  seems  to  be  endangered.  For 
it  should  be  well  kept  in  mind  that  ergot  contains  substances  which 
of  themselves  are  capable  of  inducing  sphacelus.  This  medicine  is 
particularly  useful  when  the  general  state  is  satisfactory  and  when 
the  hemorrhage  to  be  combated  is  confined  to  one  viscus.  The 
author  has  obtained  satisfactory  results  in  the  treatment  of  henior- 
raghic  nephritis,  particularly  that  form  folio  whig  scarlatina.  Two 
grams  of  Bonjean's  ergotin,  or  1  gram  of  Yvon's  solution  of  ergot, 
or  1  mg.  of  Tanret's  ergotinin  may  be  prescribed.    The  author  gen- 


790  ISFECTIOUS  DISEASES. 

erally  gives  one  gram  of  the  solution  of  ergot  for  three  days  in  suc- 
cession. This  medicine  has  the  advantage  of  diminishing  hematuria 
and  inducing  abundant  diuresis,  which  assures  organic  depuration. 
Its  action  appears  to  the  author,  however,  to  be  less  certain  and 
constant  than  that  of  calcium  chloride,  to  which  he  now  gives  pref- 
erence. 

Ipecac  is  said  to  favor  coagulation  by  modifying  pressure,  viz.,  by 
reducing  it.  This  medicine  is  applied  particularly  in  hemoptysis. 
Ten  centigrams  are  given  every  half  hour,  amounting  to  two  or  three 
grams  for  the  twenty-four  hours.  When  the  seat  of  the  hemorrhage 
is  accessible,  certain  substances  which  promote  hemostasis,  either  by 
inducing  vasoconstriction  or  by  stimulating  coagulation  of  the  blood, 
may  be  deposited  upon  it.  The  former  effect  may  be  secured  by  the 
application  of  very  cold  or  very  hot  fluids.  Cold  injections  of  water 
as  well  as  hot  injections  at  118.4°  or  122°  F.  (48°  or  50°  C.)  are 
daily  employed  against  uterine  hemorrhages.  They  may  likewise 
be  resorted  to  for  combating  nasal  hemorrhages.  Hot  enemas  also 
may  be  given.  When  hemorrhages  occur  on  the  surface,  heat  may 
be  applied  in  the  form  of  a  hot-air  current.  This  method  is  very 
efficacious. 

Cold  may  likewise  be  employed.  When  the  blood  proceeds  from 
a  deep-seated  organ  it  suffices  to  apply  upon  the  corresponding 
region  an  ice-bag.  Fredericq's  experiments  tend  to  demonstrate 
that  cold  rapidly  induces,  by  reflex  action,  vasoconstriction  of  parts 
subjacent  to  that  which  receive  the  influence.  Thus  an  anemia 
eminently  favorable  to  coagulation  is  produced.  Certain  medicines 
act  as  local  vasoconstrictors,  and  among  the  number  is  antipyrin. 
When  dusted  upon  a  bleeding  mucous  membrane,  antipyrin  often 
arrests  the  flow  of  the  blood,  and  thus  renders  great  service  in  com- 
bating nasal  or  uterine  hemorrhages. 

Caustics  form  a  transition  between  the  two  groups  of  hemostatic 
medicines,  since  they  produce  vascular  constriction  and,  coincidently, 
favor  coagulation  by  precipitating  albumins.  Hemorrhage  may  be 
arrested  by  touching  the  diseased  part  with  silver  nitrate  or  by 
placing  upon  it  a  compress  saturated  with  zinc  chloride  solution. 
The  substance  most  frequently  employed  for  this  purpose  is  per- 
chloride  of  iron;  but  it  is  gradually  falling  into  disfavor,  because 
solutions  of  it  induce  necrosis,  and  mortification,  and  small  sloughs, 
which  may  hinder  evolution  of  the  disease.  Among  the  astringents 
employed  as  hemostatics  we  may  also  cite  alum,  which  represents 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  7!i| 

the  most  active  principle  of  Pagliari'   heme  tatic   olution  (alum  l". 
benzoin  -r)0,  water  LOO). 

The  astringents  of  vegetable  origin  eem  to  be  free  from  the  inc 
veniences  inherenl  in  mineral  astringents.  The  mo  >  important  i- 
tannin,  which  may  be  used  in  its  pure  tate,  or  various  substances 
in  which  it  is  found,  [njections  and  irrigations  with  an  effusion  of 
walnut  leaves  are  often  employed  to  arre  I  lighl  hemorrhages.  I' 
is  necessary  to  remember  thai  tannin,  which  i  iconstrictor  in 

small  doses,  becomes  a  vasodilator  in  large  'lose.--,  it  may  be  em- 
ployed m  vaginal  Injections  and  enemas.  The  preparations  of  rhat- 
ania  may  often  be  substituted  for  it,  the  rool  containing  13  \<<-r  cent . 
of  tannin.  In  cases  of  intesl inal  hemorrhages  in  the  course  of  variola 
the  author  has  obtained  excellent  result.-  by  giving  large  enemas  of 
500  grams  (I  pint)  of  boiled  salt-water  containing  6  grams  ,~ 
extract  of  rhatania  morning  ami  evening.  A  new  method,  iriit i 
by  Dr.  Carnot,  consists  in  increasing  the  coagulability  of  the  blood 
by  spreading  gelatin  solutions  upon  the  diseased  surfaces.  Thifi  sub- 
stance possesses  the  double  advantage  of  heing  hemostatic  and  of 
representing  a  sort  of  aliment  for  the  cells  of  the  organism.  It  has 
the  inconvenience  of  being  a  good  culture  medium  for  microbes. 
Hence,  some  antiseptic  is  often  associated  with  it  :  0.5:  1000  solu- 
tion of  corrosive  sublimate,  or  a  few  drops  of  formol  are  added  to  the 
gelatin  solutions,  thus  rendering  them  absolutely  unassailable  by 
bacteria.  To  obtain  efficacious  hemostatic  action,  it  is  necessary  u> 
employ  a  10  per  cent,  gelatin  solution  and  sterilize  it  twice  at  212°  F. 
(100°  C.)  for  fifteen  minutes  each  time.  Care  should  be  taken  not 
to  raise  the  temperature  too  high,  otherwise  the  gelatin  will  lose  its 
characteristic  property  and  become  a  liquid.  These  solutions  are 
employed  either  in  local  applications  upon  a  bleeding  wound  or 
mucous  membrane,  or  in  intranasal  or  intravaginal  injections.  The 
author  has  frequently  utilized  vaginal  injections  of  gelatin  water  in 
the  treatment  of  metrorrhagias  which  are  so  common  and  often  grave 
in  variola.  Owing  to  the  addition  of  corrosive  sublimate  he  has 
never  observed  the  slightest  infectious  accident.  It  may.  therefore, 
be  concluded  that  gelatin  is  an  excellent  local  hemostatic.  AYhile 
the  author  has  expressed  some  reservation  concerning  its  action  upon 
multiple  hemorrhages  and  regarding  the  inconvenience,  at  least  in 
certain  cases,  of  its  subcutaneous  introduction,  there  can  be  no  doubt 
as  to  its  efficacy  in  local  treatment. 

There  is  another  substance  which  arrests  hemorrhages  admirably, 


7512  INFECTIOUS  DISEASES. 

that  is,  peroxide  of  hydrogen.  A  compress  saturated  with  the 
commercial  solution  is  applied  to  the  bleeding  part.  The  acid  con- 
tained in  the  liquid  favors  hemostasis,  but  renders  the  treatment 
somewhal  painful. 

Bv  means  of  the  various  procedures  above  indicated,  it  is  possible 
to  successfully  combat  diverse  hemorrhages.  It  is  well  to  remark, 
however,  that  this  is  simply  struggling  against  a  symptom,  against 
the  result  of  an  infectious  disease  upon  the  gravity  of  which  prog- 
nosis entirely  depends.  It  is  certain  that  in  hemorrhagic  variola 
the  gravity  is  not  due  to  the  hemorrhages.  They  simply  express 
the  profound  intoxication  to  which  the  organism  succumbs.  On 
the  other  hand,  when  a  hemorrhage  results  from  a  focal  lesion,  the 
latter  being  too  intense  or  too  profound,  hemostatics  are  then 
directed  against  the  very  cause  of  the  accidents.  All  those  that 
we  have  mentioned  are  useful,  but  it  is  evident  that  the  ideal  treat- 
ment is  surgical.  The  bleeding  vessels  should  be  ligatured.  Surgical 
applications,  however,  are  seldom  available  in  the  hemorrhages  of 
infectious  diseases.  The  attempts  that  have  been  made  in  typhoid 
fever  are  far  less  rational  and  efficacious  than  the  operations  directed 
against  perforations.  The  fact  is  that  a  large  ulcerated  vessel  is 
seldom  found.  In  most  cases  the  hemorrhages  are  multiple  or 
capillary,  and  operation  is  evidently  out  of  the  question.  Surgical 
intervention  is  serviceable  only  in  chronic  infections.  In  cases  of 
renal  tuberculosis,  nephrectomy  has  often  been  the  only  remedy 
for  the  persistent  hemorrhages. 

[  Therapeutics  of  Fever. 

Fever  constitutes  such  an  essential  feature  of  acute  infectious 
diseases,  and,  by  its  course,  generally  expresses  so  faithfully  their 
evolution  that  physicians,  mistaking  the  effect  for  the  cause,  have 
at  all  times  striven  to  check  the  febrile  movement.  Modern  advances 
in  pathological  physiology  enable  us  to  better  comprehend  the 
succession  of  events.  Hence,  the  question  whether  fever  should  be 
combated  was  laid  before  the  last  International  Medical  Congress. 

In  order  to  give  a  solution  to  this  important  problem  of  thera- 
peutics, we  must  carefully  distinguish  the  febrile  process,  viz.,  the 
increase  in  the  intraorganic  chemical  acts,  from  its  most  apparent 
result,  that  is,  hyperthermia.  To  oppose  the  chemical  metabolism 
going  on  within  an  infected  organism  would  be  checking  a  salutary 


THEBAPETJTIOB  OF  INFECTIOUS  DISEASES.  793 

reaction    salutary  ii,i;  leasl  in  mo  I  case  .  for,  a    we  ba1 1  repeatedly 
stated,  the  organism  does  tiol  alwaj    exactly  proportion  il 
to  its  needs,    [t  is  at  limes  necei  ai     to  moderate  the  inten  il 
chemical  changes.  For  this  purpose  antipyretics  render  mosl  valuable 
service.    This  is  what  occurs  especially  a1  the  end  of  infection!  and 
during  convalescence.     Il  seems  thai  the  nervou  cited 

bythe  disease  which  had  jusl  terminated, has  become  too  ensitive; 
the  slightest  cause  gives  rise  to  a  febrile  reaction  which  muei  be 
combated,  notably  by  antipyrin. 

In  the  course  of  acute  infections  antipyretics  are  generally  pre- 
scribed only  when  they  can  acl  upon  the  cause  of  the  fever.  Specifics 
respond  to  this  indication.  The  type  of  this  cla  i  represented  by 
quinine  sails.  It  is  lo-day  admitted  thai  these  salts  are  extremely 
toxic  for  the  protozoa.  They  arrest  the  evolution  of  Laveran's 
parasites,  and  consequently  the  reaction  which  characterizee  the 
paroxysm.  It  would  be  an  error  to  say  thai  quinine  is  an  anti- 
pyretic. It  prevents  the  return  of  the  fever  because  it  arrests  the 
infectious  process  which  causes  it.  Hence,  it  produces  no  net  inn 
against  the  majority  of  other  hyperthermias.  Knonnous  dosi 
quinine  have  been  given  to  typhoid  and  tubercular  patients  withoul 
lowering  their  temperature  so  much  as  one-tenth  of  a  degree. 

Salicylate  of  soda  seems  to  act  in  the  same  manner.  It  extin- 
guishes rheumatic  fever  because  it  cheeks  the  infectious  process. 
It  is  the  same  with  mercury  and  iodide,  which  combat  syphilitic 
fever.  To  speak  of  antipyretics  in  all  such  cases  would  be  no  more 
exact  than  to  speak  of  an  antipyretic  operation  when  a  pyogenic 
fever  is  arrested  by  opening  a  suppurating  focus.  The  fever  is 
suppressed  because  the  cause  of  the  accidents  has  been  removed. 

Although  in  the  majority  of  cases  it  would  be  a  mistake  to 
combat  the  febrile  process,  it  should  not  be  concluded  that  it  is 
contraindicated  to  combat  its  principal  result — hyperthermia.  I 
have  endeavored  to  make  it  clear  that  elevation  of  temperature  is 
the  result  and  sign  of  increased  activity  in  the  chemical  acts.  A 
larger  amount  of  heat  is  produced,  but  the  excess  is  at  the  same 
time  dissipated,  as  is  proved  by  the  increased  radiation  of  heat. 
It  is,  therefore,  indicated  to  combat  hyperthermia  by  increasing 
radiation.     The  best  method  is  by  cold  bathing. 

Cold  and  Lukewarm  Baths.  From  the  earliest  antiquity  baths 
have  been  given  in  certain  infections.  A  lukewarm  bath  was  com- 
monly employed,  notably  in  pneumonia.     It  was  also  a  lukewarm 


794  INFECTIOUS  DISEASES. 

bath  that  was  first  employed  against  typhoid  fever  by  Currie  in 
the  eighteenth  century,  and  at  the  beginning  of  the  nineteenth 
by  Chomel,  Recamier,  and  Rayer.  Cold  water  had,  however, 
already  been  praised  by  Bartholin,  more  than  two  hundred  years 
ago,  against  pneumonia.  The  method,  however,  does  not  seem  to 
have  had  great  success,  for  about  fifty  years  ago  physicians  timidly 
utilized  cold  lotions,  and  sprinkling,  and  the  wet  sheet.  Few  of 
them  ventured  to  bathe  then  fever  patients.  A  few  attempts  were 
made  in  favor  of  cold  baths  by  Giannini  (1805),  Chomel,  Recamier, 
Jacquez  and  Leroy.  It  was,  however,  only  after  the  labors  of  von 
Ziemssen  and  Brand  (1861)  that  antipyretic  balneotherapy  entered 
into  therapeutics  in  a  definite  manner. 

Yon  Ziemssen  prescribed  baths  that  rendered  the  body  gradually 
colder.  Bouchard  adopted  a  similar  method.  In  order  to  avoid 
the  influence  exerted  upon  the  nervous  system  and  the  vasocon- 
strictors by  cold  wrater,  he  caused  the  patient  to  be  placed  in  a  bath 
the  temperature  of  which  is  only  two  degrees  Centigrade  lower  than 
that  of  the  body.  Then  he  progressively  lowers  the  temperature 
of  the  bath  to  86°  F.  (30°  C),  never  below  that  point. 

By  the  method  which  bears  his  name,  Brand  produces  a  violent 
excitation  of  the  nervous  system.  Let  us  consider  the  rules  laid 
clown  by  him  for  the  treatment  of  typhoid  fever.  They  are  appli- 
cable, with  slight  modifications,  to  all  infectious  diseases. 

As  soon  as  the  temperature  of  the  patient  exceeds  102.2°  F. 
(39°  C),  he  is  plunged  into  a  bath  at  68°  F.  (20°  C);  at  times, 
if  the  case  is  grave  and  the  fever  intense,  into  a  bath  at  64.4°  F. 
(18°  C).  Certain  precautions  are  to  be  taken  at  the  same  time. 
Borated  vaseline  is  applied  to  abrasions  and  pustules.  In  order  to 
avoid  too  violent  respiratory  disturbance,  cold  effusions  are  applied 
to  the  face  and  chest,  and  the  patient  is  then  taken  in  the  arms  of 
the  nurse  and  placed  in  the  bath-tub.  The  tub  should  contain 
sufficient  wrater  to  cover  the  shoulders,  and  it  is  advisable  to  renew 
the  water  for  each  bathing.  When  the  patient  is  in  the  bath-tub 
he  receives  three  cold  effusions  at  50°  F.  (10°  C),  at  the  nape  of 
the  neck.  These  effusions  should  last  three  minutes  each.  Frictions 
upon  the  body,  except  the  abdomen,  are  at  the  same  time  to  be 
made.  Finally,  a  small  amount  of  vinous  lemonade  is  to  be  given 
to  the  patient.  The  bath  lasts  fifteen  minutes.  If  he  should  experi- 
ence chills  the  patient  may  still  be  left  in  the  water,  but  not  for 
more  than  two  or  three  minutes  longer.     When  once  out  of  the 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

water  he  must  be  rapidly  wiped   and  then  enveloped  in  blai 
and  warmed  by  means  of  hoi  water  bag    applied  to  the  leg    and 
feet.    Half  an  hour  later  he  must  be  given  milk  and  bouillon. 

[f  the  patient  does  uol  sleep,  or  if  his    leep  i    agitated,  Brand 
advises,  during  the  intervals  of  the  baths,  application  of  compr<    e 
of  water  at  50°  F.  (10°  C.)  to  the  chesl  and  abdomen,  to  be  renewed 
(^vcry  five,  ten,  or  fifteen  minutes,  according  to  the  intensity  of  the 
lover.    Tripier  and  Bouverel  prefer  large  cold  poultices  upon  the 
abdomen.   The  bathing,  to  be  efficacious,  musl  be  instituted  at 
as  the  diagnosis  of  typhoid  fever  is  made.     It  there  i-  any  doubt 
as  to  the  nature  of  the  disease,  bathing  may  still  be  resorted  to, 
provided  it  is  discontinued  if  further  developments  prove  the 
not  to  be  typhoid.    When  the  physician  i-  called  to  the  side  of  a 
patient  who  has  been  suffering  from  typhoid  fever  for  three  Wi 
the  cold  biitl  1  is  useless,  and  Brand  himself  then  prefers  lukewarm 
baths. 

The  baths  must  be  started  as  scion  as  the  temperature  of  the 
patient  reaches  102.2°  F.  (39°  C),  and  the  temperature  musl  con- 
stantly guide  the  physician.  The  temperature  must  be  taken  every 
three  hours.  When  it  rises  above  102.2°  F.  (39°  C.)  a  bath  is  given. 
When,  at  the  end  of  three  hours,  the  temperature  has  not  risen  to 
that  point,  the  corresponding  bath  is  omitted.  The  case  is  to  be 
managed  in  this  manner  until  the  fever  falls  below  102.2°  F.  (39°  C.) 
definitively.  At  the  beginning  the  temperature  rises  quite  rapidly. 
The  patient,  therefore,  takes  the  baths  regularly  every  three  hours. 
As  they  are  not  interrupted  during  the  night,  he  consequently  Takes 
eight  baths  a  day.  Later  he  skips  several.  In  certain  cases  fever 
is  very  intense  and  does  not  yield  to  balneotherapy.  Brain  1  then 
advises,  in  addition,  the  permanent  employment  of  cold  comprt  3sefi 
Tripier  and  Bouveret  resort  to  the  wet  sheet.  Chauffard  gives  the 
baths  at  shorter  intervals;  Juhel-Renoy  gives  one  every  two  hours 
at  59°  to  60.8°  F.  (15°  to  16°  C). 

In  typhoid  fever  cold  bathing  has  a  certain  number  of  contra- 
indications. In  the  first  place,  age  is  to  be  taken  into  account. 
In  children  above  two  years  of  age  it  is  well  to  begin  with  baths 
at  77°  F.  (25°  C);  below  that  age.  lukewarm  baths  at  86°  or  89.6°  F. 
(30°  or  32°  C.)  must  be  given  three  or  four  times  in  twenty-four 
hours,  each  lasting  from  five  to  eight  minutes.  Brand  does  not 
advise  cold  bathing  if  the  patient  is  more  than  fifty  years  old. 
According  to  my  personal  observations.  I  believe   that  this  limit 


796  INFECTIOUS  DISEASES. 

should  be  lowered.  It  may  broadly  be  stated  that,  in  all  infections, 
cold  baths  are  dangerous  above  forty  years  of  age.  They  may, 
nevertheless,  be  employed  at  this  age  if  the  circulatory  and  the 
respiratory  apparatus  of  the  individual  are  in  a  perfect  state.  As 
a  matter  of  fact,  before  instituting  balneotherapy,  the  physician  must 
carefully  examine  these  two  apparatuses.  Valvular  lesions  of  the 
heart,  chronic  myocarditis  and  pericarditis,  arteriosclerosis,  as  well 
as  chronic  bronchitis,  dilatation  of  the  bronchi,  tuberculosis,  and, 
above  all,  pulmonary  emphysema,  are  contraindications  to  the 
balneotherapic  method,  even  to  the  method  of  graduated  cold  baths. 
Next,  the  nervous  system  must  be  taken  into  account.  In  hysterical 
individuals  the  bath  may  provoke  an  attack.  In  that  case  it  must 
be  discarded.  In  certain  neuropathic  persons  it  causes  fainting  or 
paroxysms  of  suffocation  with  a  certain  degree  of  asphyxia  and 
cyanosis.  In  such  cases  a  cold  bath  is  likewise  contraindicated. 
Moreover,  some  patients  have  such  repugnance  to  bathing  that 
after  they  have  been  given  one  their  temperature  is  not  lowered, 
but,  at  times,  even  a  rise  occurs.  By  insisting  a  little,  the  physician 
sometimes  may  render  the  bathing  method  acceptable  to  such 
individuals;  otherwise,  it  is  better  to  abandon  the  balneotherapic 
procedure. 

These  "considerations  are  applicable  to  all  infections.  Here  are 
some  concerning  particularly  typhoid  fever :  Intestinal  hemorrhages 
and  peritoneal  manifestations  demand  absolute  rest,  and  baths  should 
therefore  be  suspended.  Pneumonia  is  not  a  contraindication,  except 
when  the  heart  shows  signs  of  weakness.  We  here  touch  a  much 
disputed  problem.  What  course  is  to  be  followed  in  cases  of  myo- 
carditis? The  perusal  of  classical  works  leaves  the  physician  in  an 
embarrassed  state  of  mind,  for  equally  competent  authorities  have 
advanced  contrary  views.  I  believe  that,  at  the  beginning,  when 
myocarditis  is  expressed  simply  by  acceleration  in  the  heart-beats 
and  weakening  of  the  pulse,  bathing  should  still  be  employed, 
provided  the  heart  is  sustained  by  medicines  such  as  caffein.  Should 
the  slightest  fainting  occur  during  the  bathing  the  method  must 
be  suspended  definitively.  If  the  myocardium  seems  to  be  affected, 
lukewarm  bathing  may  be  tried;  if  it  is  well  borne,  the  succeeding 
baths  may  be  given  gradually  colder.  At  a  more  advanced  period, 
when  auscultation  reveals  a  bruit  de  galop,  and  especially  the  fetal 
rhythm,  then  balneotherapy  seems  to  be  a  dangerous  method,  for 
the  reason  that  the  movements  of  the  patient  may  provoke  syncope 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  7!i? 

and  sudden  death.   The  writer  believe  that,  under  such  condition  . 

all  kinds  of  baths  should  be  avoided. 

Cold  baths  do  not  abridge  the  duration  of  typhoid  fever,  buf  they 
palliate  certain  symptoms  and   dimini  h  the  death  rate.    Tnere  it 
little,  if  any,  stupor;  the  tongue  is  moist,  diarrhea  if  model 
diuresis  is  more  abundant,  the  appetite  i    qoI  completely  lo 
that  the  patient  takes  nourishment  with  pleasure.    Delirium  it 
and,  instead  of  somnolence  and  the  muttering  observed  in  ordinar) 
cases,  the  patient  enjoys  a  quid  and  refreshing  sleep  after  a  bath. 

The  course  of  the  temperature  is  profoundly  modified.  Brand 
divides  it  into  three  periods:  the  period  of  resistance,  during  which 
the  temperature  is  but  slightly  modified:  then  the  period  of  re- 
mission, and,  finally,  thai  of  defervescence.  The  longer  the  firsl 
period  lasts,  the  longer  and  more  rebellious  will  be  the  case.  If  the 
temperature  yields  to  the  first  baths,  the  fever  to  be  deall  with  will 
prove  to  be  a  mild  one.  The  cold  hath  also  aets  upon  the  circulation 
and  respiration;  it  stimulates  the  action  of  the  heart  and  strengthens 
the  pulse;  it  diminishes  bronchitis  and  relieve-  pulmonary  con- 
gestion. 

As  already  stated,  the  death-rate  is  considerably  reduced  by  this 
treatment.  It  is  not  necessary  to  cite  numerous  statistics;  it  will 
suffice  to  state  that  out  of  19,017  observations  tabulated  by  Brand 
the  mortality  did  not  exceed  7.S  per  cent.  In  the  Bavarian  army, 
in  which  the  method  is  practised  in  all  its  rigor  and  is  instituted  as 
soon  as  the  disease  is  suspected,  the  death-rate  reaches  hardly 
1  per  cent.  Although  cold  baths  are  at  present  frequently  employed 
according  to  the  rules  of  Brand,  they  have  often  been  modified. 
Thus,  the  employment  of  baths  at  82.4°  F.  (28°  C.)  has  gradually 
become  the  current  practise  in  the  hospitals  of  Paris.  The  baths 
are  given  every  three  hours,  when  the  temperature  exceeds  102  ,2 
or  103.1°  F.  (39°  or  39.5°  C).  When  baths  at  82.4°  F.  (28°  C.) 
are  given,  it  is  useless  to  employ  previous  cold  effusion?  or  friction 
during  the  bath.  This  method  is  more  readily  accepted  by  the 
patients,  it  requires  less  caution,  and  gives  satisfactory  result-  ! 
have  recourse  to  it  in  benign  cases,  and  I  employ  no  other  in  the 
case  of  children. 

Cold  baths  do  not  act  merely  by  abstracting  heat.  On  the  con- 
trary, their  action  is  far  more  complex.  This  question  has  been 
well  studied  by  Liebermeister.    We  borrow  from  him  the  following 


798  INFECTIOUS  DISEASES. 

figures,  which  show  the   difference  of  action  of  a  bath  at  71.6°  F. 
(22°  C.)  from  that  at  82.4°  F.  (28°  C.) : 


In  a  i 

Bath 

U 

lit  a 

Bath  at 

71.6°  F. 

(22° 

C). 

S2.4°  F.  (28°  C.) 

In     5 

mii 

Utes  the  patient 

Loses    . 

.    122  calorie 

s. 

33  calories. 

In  10' 

"            "             " 

" 

.    1G5 

tt 

44 

" 

In  15 

"    •        " 

" 

.    192 

a 

50 

tt 

In  2U 

"            "             " 

.    20S 

" 

52 

" 

In  30 

,1              u               tt 

" 

.    342 

" 

56 

tt 

If  the  principal  object  was  to  abstract  heat,  the  bath  at  82.4°  F. 
(28°  C.)  should  be  rejected  without  hesitation;  but  at  present  the 
influence  of  hyperthermia  is  no  longer  so  much  dreaded.  It  is  known 
that  the  disturbances  and  lesions  formerly  attributed  to  high  temper- 
ature are  in  most  cases  due  to  toxins.  Cold  baths  produce  satis- 
factory results,  not  merely  by  lowering  the  temperature,  but  exercis- 
ing a  favorable  influence  upon  the  various  apparatus  of  the  entire 
organism.  First  of  all,  the  nerve  terminations  of  the  skin  are  influ- 
enced by  the  bath,  and  their  dynamic  modification  reaches  the 
centres.  The  very  cold  bath  thus  gives  rise  to  a  violent  excitation ; 
the  lukewarm  bath  has  a  sedative  action .  In  both  cases  the  function 
of  the  nervous  system  is  regulated,  and  amelioration  in  the  activity 
of  all  the  tributary  organs  results.  The  heart  largely  participates 
in  the  benefit  of  this  happy  influence.  In  the  case  of  cold  baths, 
the  cutaneous  vasoconstriction  raises  the  blood  pressure,  and  thus 
modifies  the  activity  of  the  myocardium.  Circulation  is,  therefore, 
favored  in  the  lungs  and  kidneys.  Hence,  diminution  in  pulmonary 
congestion  and  increase  in  diuresis,  as  well  as  greater  activity  in 
general  oxidation,  result.  All  these  changes  explain  how  the  bath 
diminishes  the  intoxication  of  the  organism.  It  accomplishes  this 
by  regulating  nutrition,  by  favoring  the  action  of  the  liver  and  the 
emunctories,  notably  the  kidneys.  The  experiments  of  Drs.  Roques 
and  Weil  demonstrated  that  the  urinary  secretion  is  not  only 
increased  in  amount  but  also  in  toxicity.  Thus  a  great  quantity 
of  toxins  is  carried  away  and  the  organism  purified. 

Brand's  method,  which  was  at  first  applied  to  typhoid  fever,  is 
now  employed  in  a  great  number  of  infections.  The  baths  may  be 
given  whenever  the  temperature  is  very  high,  not  so  much  because 
of  the  hyperthermia  as  for  the  intensity  of  the  morbid  phenomena 
which  produce  and  entertain  it.  The  baths  must  likewise  be  resorted 
to  when  the  nervous  system  is  profoundly  affected,  when  the  pulse 
is  very  rapid  and  the  urine  scanty.     The  physician  must  always 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  799 

be  guided  by  the  gravity  of  the  phenomena  in  choosing  bel 
Lukewarm,  82.4°  F.  (28°  C),  and  cold  baths,  69°  or  64  1    I      20 
18°  C).    The  latter  are  especially   indicated   when   the  nei 
system  is  profoundly  affected,   whether  the  phenomena   indicate 
depression,  or,  on   the  contrary,  too  violenl  excitation  .   juch  as 
delirium  tremens,  are  present.    Finally,  the    ati  factorj  re  ultt  ob- 
tained by  cold  baths  in  the  treatment  of  cerebral  rheumatism  I 
long  been  recognized . 

En  our  hospital  we  employ  the  bath  at  82.4    I.    .'-    I  fre- 

quently at  a  lower  temperature,  in  case  oi  carlatina  and  erysipelas 
whenever  the  temperature  remains  longer  than  usual  around  or 
above  104°  F.  (40°  ('.).  This  treatmenl  ie  let  frequently  available 
in  measles,  for  the  gravity  of  the  latter  disi  ase  depends  simply  upon 
pulmonary  complications.    We  Bhall  again  refer  to  this  subject. 

Balneotherapy  is  nlso  indicated  in  measles,  scarlatina,  and  variola 
when  the  eruption  is  not  well  developed.  The  author  prefer.-  warm 
baths  at  89.6°  or  93.2°  F.  (32°  or  .34°  C),  and  in  grave  variola 
or  measles,  mustard  baths.  At  the  beginning  of  all  eruptive  fevers 
we  frequently  see  serious  general  manifestations  while  the  eruption 
is  as  yet  hardly  noticeable.  The  eruption  does  not  come  oul  as 
rapidly  and  with  the  same  intensity  as  in  fortunate  cases.  A  few- 
baths  hasten  the  appearance  of  the  exanthema  and  palliate  the  grave 
symptoms.  In  variola  also,  as  we  have  already  stated,  excellent 
results  are  obtained  by  the  same  method.  The  author  gives  luke- 
warm baths  to  which  some  corrosive  sublimate  or  naphthol  is  added. 
Notwithstanding  its  lesions,  the  skin  bears  this  mode  of  treatmenl 
well.  It  exercises  a  marked  action  upon  the  pyogenic  bacteria  which. 
at  a  certain  period  of  evolution,  invade  the  pustules. 

Among  the  infections  for  which  baths  are  available  there  are  three 
which  require  special  attention.  These  are  scarlatina,  pneumonia, 
and  erysipelas.  Hyperpyretic  scarlatina  is  generally  described  as  the 
type  of  malignant  scarlatina.  If  we  refer  to  our  statistics  we  find 
that  the  frequency  of  this  form,  at  least  in  the  adult,  lias  been  some- 
what exaggerated.  We  have  received  in  our  wards,  especially  in  1 899, 
grave  cases,  several  of  which  rapidly  ended  in  death.  In  the  majority 
of  the  cases,  however,  the  temperature  was  not  extremely  high.  It 
is  not,  therefore,  safe  to  be  guided  exclusively  by  the  course  of  the 
temperature.  The  general  state  of  the  patient  furnishes  more  reli- 
able indications.  The  general  state  likewise  directs  the  therapeutics 
of  pneumonia.     All  grave  cases  must  not.  however,  be  indiscrimin- 


800  INFECTIO  US  DISEASES. 

ately  treated  by  baths.  This  medication  must  not  be  resorted  to  in 
the  aged  or  in  arteriosclerotic  individuals,  or  those  suffering  from 
heart  lesions  and  Bright  's  disease.  These  are  substantially  the  same 
contraindications  which  we  have  pointed  out  with  regard  to  other 
diseases.  The  reason  we  emphasize  the  point  is  that  it  is  precisely 
under  these  conditions  that  the  gravest  cases  are  observed  and  that 
the  physician  is  tempted  to  prescribe  baths.  What  is  more  peculiar 
to  pneumonia  is  the  danger  of  giving  rise  to  collapse  in  case  both 
lungs  are  involved.  In  fortunate  cases,  under  the  influence  of  the 
bath,  respiration  becomes  easier,  expectoration  more  profuse  and 
free,  cyanosis  disappears,  and  diuresis  is  more  marked;  at  times  a 
veritable  polyuria  is  produced.  Hence  the  termination  of  the  disease 
differs  from  that  observed  when  the  evolution  is  left  to  itself.  The 
crisis  is  replaced  by  a  slow  defervescence,  which  is  probably  clue  to 
the  fact  that  the  toxins,  far  from  being  accumulated  during  the 
disease,  to  be  suddenly  rejected  at  the  moment  of  the  termination, 
have  been  eliminated  in  a  continuous  manner. 

Baths  are  currently  employed  in  the  treatment  of  bronchopneu- 
monia. In  this  case  cold  baths  have  been  almost  entirely  abandoned, 
for  they  readily  give  rise  to  collapse,  especially  in  young  children. 
Graduated  cold  baths  may  be  used.  They  may  be  given  at  two 
degrees  lower  than  the  temperature  of  the  patient  and  progressively 
lowered  to  82.4°  F.  (28°  C).  Their  duration  must  not  exceed  five 
minutes.  More  frequently  lukewarm  mustard  baths  are  prescribed, 
especially  for  children.  Finally,  since  the  contributions  of  Dr. 
Renaut,  warm  baths  at  100.4°  F.  (38°  C.)  are  often  employed.  The 
child  remains  in  it  from  ten  to  twenty  seconds,  and  during  all  this 
time,  cold  compresses  are  applied  to  the  head.  The  baths  rapidly 
palliate  the  bronchial  manifestations,  but  they  produce  hardly  any 
effect  upon  the  pulmonary  lesions.  Their  action  upon  the  general 
state  is  excellent,  but  the  hot  bath  is  somewhat  depressing.  It  must 
be  avoided  in  adynamic  cases  or  when  cardiac  disturbances  are 
present. 

The  author  frequently  employs  lukewarm  baths  in  the  treatment 
of  erysipelas.  In  cases  of  circumscribed  erysipelas  of  the  face  unat- 
tended by  grave  general  phenomena  the  bath  is  useless.  In  spite 
of  the  temperature  of  104°  F.  (40°  C.)  defervescence  is  rapidly  pro- 
duced. If,  however,  fever  persists,  if  certain  alarming  manifesta- 
tions, such  as  adynamia,  delirium,  and  agitation  are  observed,  or  if 
the  inflammatory  lesion  spreads,  a  bath  at  82.4°  F.  (28°  C.)  should 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  -■.] 

I, hen  be  given  every  three  hour,  whenever  the  temperatun 
L03°  F.  (39.5°  C). 

In  cases  of  wandering  erysipelas,  bath    al  82.5'    I       '      '      are 
likewise  indicated.    They  should  be  given   ;   tematically  every  three 
hours,  regardless  of  fluctuations  in  the  temperature,  for  in  * 
wandering  forms  very  wide  oscillation   are  observed,  and  even  inter- 
mittent types  are  sometimes  encountered.    Bathi  are  similarly 
cessful  in  delirium.    The  author  generally  employs  lukewarm  baths. 
Morning  and  evening  he  prescribes  a  bathal  93.2    I     34  C),  which 
lasts  from  thirty  i<>  forty-five  minutes.    Its  sedative  effecl  upon  the 
nervous  system  is  very  remarkable.    Warm  bathe  succeed  very  well 
in  erysipelas  of  children  :m<l  of  the  newborn.    In  the  latter,  regard- 
less of  the  seat  of  the  lesion,  three  daily  baths  al  89.5   oi  93.2    I  . 
(32°  or  34°  C),  lasting  six  or  eigbl   minutes,  constitute  the 
method. 

It  is  well  to  once  more  recall  the  danger  of  baths  for  individuals 
above  forty  years  of  age.  As  erysipelas  is  a  disease  occurring  mainly 
after  this  age,  the  author  believes  the  following  precept  should  be 
emphasized:  lukewarm  baths  may  be  given  between  the  agi 
forty  and  fifty  years;  after  fifty  years  they  should  not  be  prescribed 
except  for  robust  individuals  presenting  no  lesions  of  the  circulatory 
or  respiratory  apparatus. 

Chemical  Antithermics.  Chemical  antithermics  ac1  in  three  ways: 
they  exercise  a  sedative  action  upon  the  nervous  system ;  they  dimin- 
ish the  protoplasmic  activity  of  the  cells:  they  modify  the  function 
of  the  red  blood  corpuscles.  Of  these  three  actions  the  firsl  is  contest- 
able; it  results  simply  from  the  fact  that  antithermics  are.  as  a  rule, 
analgesics.  The  second  is  bad,  for  increased  functional  activity  of 
the  cells  represents  a  necessary  reaction  which  should  be  modei 
only  under  certain  circumstances.  The  third  is  worse,  for  it  consists 
in  the  formation  of  methemoglobin,  which  causes  cyarn  »sis.  This  last 
influence  is  particularly  manifest  when  kairin,  thallin.  or  acetanilid 
(antifebrin)  are  employed.  These  products  are.  therefore,  ab  si 
completely  abandoned,  and  only  three  antipyretics  are  at  present 
made  use  of:  quinine,  antipyrin.  and  salicylic  acid  and  its  derivatives. 

The  successes  obtained  by  quinine  in  the  treatment  of  malarial 
fevers,  in  which  it  acts  as  a  specific,  have  too  easily  led  to  the  belief 
that  this  substance  is  a  universal  febrifuge.  In  typhoid  fever  as  well 
as  in  erysipelas,  pneumonia,  and  variola,  the  author  has  repeatedly 
observed  that  large  doses  of  quinine  salts  may  be  administered  with- 

51 


802  IXFECTIO  US  DISEA  SES. 

out  producing  any  noticeable  change  in  the  temperature.  One  gram 
and  a  half  or  two  grams  are  required  in  typhoid  fever  in  order  to  effect 
a  reduction  of  temperature.  In  view  of  these  failures,  some  authors 
have  stated  that  quinine  regulates  rather  than  lowers  the  tempera- 
ture. Its  administration  must,  Therefore,  be  reserved  for  those  cases 
of  fever  which  present  wide  oscillations — i.  e.,  fevers  of  an  intermit- 
tent type,  like  malarial  fever.  This  remark  is  correct  for  some  cases. 
Thus,  for  instance,  in  typhoid  fever,  after  having  remained  at  a 
certain  point  during  the  stationary  period,  the  temperature  often 
presents  wide  oscillations  at  the  moment  of  termination.  When 
fever  is  continuous  the  author  has  never  found  quinine  efficacious. 
At  the  time  of  the  oscillations  the  administration  of  this  alkaloid 
appeared  in  some  cases  to  bring  the  temperature  to  the  normal. 
Hence,  the  author  believes  that  it  is  useless  to  prescribe  quinine 
during  the  stationary  period.  This  medicine  should  be  reserved  for 
the  third  period.  If  the  temperature  then  presents  an  amphibole 
stage  and  does  not  return  to  the  normal,  quinine  should  be  prescribed 
in  decreasing  doses  for  three  days  in  succession,  four  or  five  hours 
before  the  expected  return  of  the  paroxysm.  The  author  prescribes 
1  gram  the  first  day,  75  eg.  the  second,  and  50  eg.  the  third  day. 
It  is  to  be  borne  in  mind,  however,  that  this  method  is  not  infallible 
and  that  quite  often  fever  does  not  yield  to  the  action  of  quinine 
even  at  this  period. 

The  author  has  likewise  been  convinced  of  the  inefficacy  of  quinine 
in  the  treatment  of  hectic  fever  of  tubercular  subjects  and  of  the 
fever  of  erysipelas,  even  when  its  course  assumes  the  intermittent 
type,  falling  to  98.5°  F.  (37°  C.)  in  the  morning,  to  rise  to  104°  F. 
(40°  C.)  in  the  evening.  Lastly,  in  symptomatic  intermittent  fevers 
quinine  at  times  lowers  the  temperature.  The  result  is  not  very 
marked  or  very  durable,  however,  so  that  this  medicine  may  serve 
to  make  a  differential  diagnosis  between  symptomatic  intermittent 
and  malarial  fevers. 

Antipyrin  has  a  far  more  marked  influence  upon  the  febrile  pro- 
cess. It  often  lowers  the  temperature;  but  it  accomplishes  this  by 
diminishing  oxidations,  consequently,  by  hindering  one  of  the  reac- 
tionary procedures  employed  by  the  organism.  Hence,  its  use  is  but 
exceptionally  indicated.  The  author  finds  only  a  few  cases  in  which 
this  medicine  is  serviceable.  The  first  is  influenza.  Antipyrin 
must  be  given  mixed  with  quinine.  The  author  prescribes  1  or  2 
grams  of   the  first  with  75   eg.  or   1  gram  of  the   second.     When 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

administered  at  the  beginning  of    influenza  bhi    medication  often 

succeeds  in  arrest ing  the  di  ea  e.     I1  i    almo  i  a    pecific.    Again, 
those  tubercular  patients  who  suffer  from  fever  are  often  benefited 

by  the  use  of  antipyrin,  al  lea  I  in  tho  •  r  ■  •  in  which  it  does  not 
cause  too  much  sweating.  Its  action  upon  the  fever  of  tubercular 
subjects  is  so  marked  thai  Dr.  Landouzy  thinks,  with  good  reason, 
that  it  may  throw  lighl  upon  a  doubtful  diagnosis  in  acute  c 
When  the  physician  is  not  sure  whether  be  is  dealing  with  a  typhoid 
lexer  or  an  acute  miliary  tuberculosis,  the  administration  "t  anti- 
pyrin,  if  it  be  followed  by  a  well-marked  defervescence,  will  lead  him 
to  assume  Mia.1  (license  is  tubercular.  At  any  rate,  antipyrin  acta 
in  all  forms  of  tubercular  fever,  even  againsl  hectic  fever.  It  -  acl  ion, 
however,  is  transitory.  The  author  has  seen  tubercular  cases  in  which 
no  treatment  had  succeeded  in  lowering  the  temperature,  become 
completely  apyretic  under  the  influence  of  this  medicine.  At  the  end 
of  four  or  five  days,  however,  fever  reappeared,  and, although  the  dose 
was  increased  to  3  and  I  grains  in  twenty-four  hours,  the  effect 
seemed  completely  exhausted.  Although  transitory  and  in  nowise 
affecting  the  process  itself,  hut  only  one  of  its  effects,  the  action  of 
antipyrin  seems  to  the  author  sufficiently  marked  to  give  the  sub- 
stance a  permanent  place  in  the  therapeutics  of  tuberculosis. 

While  antipyrin  is  useless  in  the  stationary  period  of  infections,  it 
renders  true  service  at  the  terminal  period  and  during  convalescence. 
In  many  cases  fever  survives  the  disease.  The  morbid  symptoms 
seem  to  have  disappeared,  but  the  temperature  does  not  become 
normal.  This  fact  is  due  to  the  reactionary  susceptibility  of  the 
organism  induced  by  the  infection.  Under  these  conditions  the 
organic  combustions  exceed  the  requirements  of  the  system.  Anti- 
pyrin, by  modifying  oxidations,  reduces  metabolism  to  a  degree  cor- 
responding to  the  wants  of  the  economy.  Likewise,  during  conval- 
escence the  slightest  cause  suffices  to  raise  the  temperature.  A  febrile 
paroxysm  may  supervene,  even  without  any  noticeable  cause. 
Antipyrin  is  then  indicated,  inasmuch  as  this  fever  of  convalescence  is 
dependent  upon  the  same  mechanism  as  the  lingering  fever  at  the  end 
of  infections,  and  should  be  treated  in  the  same  maimer. 

A  new  antipyretic,  pyramidon,  has  recently  been  praised,  and  may 
be  employed  under  the  same  conditions  as  antipyrin.  but  in  smaller 
doses.  This  substance  has  given  satisfactory  results  in  some  of  the 
author's  cases.  Its  advantage  consists  in  its  very  quick  elimination. 
Thirty  and  fifty  centigrams  of  pyramidon  may.  therefore,  be  pre- 


804  ISFECTIO  US  DISEASES. 

scribed  every  three  hours,  and  as  much  as  two  grams  a  day  without 
fear  of  any  untoward  cumulative  effects. 

Salicylic  acid  and  its  derivatives — salol,  salophen,  salipyrin,  and 
aspirin — are  often  classed  with  antipyretics.  Salicylate  of  soda  lowers 
the  temperature  in  cases  of  rheumatic  polyarthritis,  but  it  is  the 
specific  of  this  infection.  On  the  other  hand,  it  is  without  effect  in 
infectious  pseudorheumatism.  It  may,  therefore,  serve  the  purposes 
of  differential  diagnosis. 

Salicylate  of  soda  and  salol  owe  certain  antipyretic  virtues  to  their 
antiseptic  properties.  Hence,  these  medicines  may  be  employed  to 
combat  certain  symptomatic  fevers,  notably  those  related  to  suppu- 
rations of  the  biliary  passages  or  the  urinary  apparatus.  In  these 
cases,  however,  the  process  is  not  a  truly  febrifuge  action.  The 
medicine  produces  its  effect  bjr  acting  upon  the  cause.  Its  adminis- 
tration is,  therefore,  clearly  indicated  and  realizes  an  etiological 
medication. 

Finally,  by  a  mechanism  as  yet  illy  elucidated,  guaiacol  when 
applied  to  the  skin  has  the  interesting  property  of  lowering  the  tem- 
perature. It  acts  so  powerfully  that,  if  precautions  are  not  taken, 
collapse  may  occur.  This  method  is  available  particularly  in  the 
treatment  of  tubercular  fever. 

Conclusion.  From  the  foregoing  brief  study  we  may  conclude 
that  there  are  no  good  antipyretic  medicines.  At  all  events,  the 
dangers  and  inconveniences  of  fever  have  been  much  exaggerated. 
In  many  cases  to  arrest  the  febrile  process  would  be  to  harm  the 
patient. 

The  true  antipyretic  is  that  which  suppresses  fever,  not  by  dis- 
turbing the  reactionary  movement  of  the  organism,  but  by  acting 
upon  the  cause  of  the  febrile  process.  This  is  precisely  what  is  real- 
ized by  specifics — quinine  in  malaria,  mercury  and  iodides  in  syph- 
ilitic fever,  sodium  salicylate  in  rheumatism,  the  insoluble  antiseptics 
in  fevers  of  intestinal  origin,  and  antiseptics  or  antitoxins  introduced 
into  infected  foci.  These  are  substances  which  deserve  to  be  con- 
sidered as  antipyretics  of  predilection.  They  act  by  combating  the 
cause  of  the  morbid  process,  while  most  of  the  febrifuges,  by  modi- 
fying the  reactionary  mechanism,  hinder  nature's  work.  Balneo- 
therapy alone  represents  a  natural  medication,  for  it  simply  favors 
dissipation  of  heat,  which  is  already  increased  by  the  disease.  At  the 
same  time  baths  act  upon  the  principal  apparatus  of  the  economy. 
Hence,  they  are  now  currently  used  and  are  applicable  to  a  great 


THEBAPEXJTIOB  OF  INFECTIOUS  DISEASES.  805 

number  of  infections.    Being  given  lukewarm  or  cold,  according  to 
circumstances,  the  bath  is  the  only  true  antipyretic  thai  may  be 

prescribed. 

Venesection. 

We  are  far  from  the  epoch  when  blood-letting  wan    j  tematically 

practised  in  fevers,  when  it  was  imagined  thai  acute  di  ea  i  could 
be  checked  by  repeated  abstraction  of  the  vital  Quid.  At  presenl 
this  method  is  seldom  resorted  to  in  the  treatmenl  of  infectious 
diseases.  II  is  employed  only  in  pneumonia  or  in  certain  complica- 
tions. Wo  nmsf,  ilierefore,  briefly  study  its  influence  upon  the 
organism  and  its  possible  indications  in  infections.  Withoul  present- 
ing the  history  of  the  physiological  effects  <  I'  blood-letting,  which  is 
still  obscure  on  cerlain  points,  it  will  suffice  to  refer  fco  the  acquired 
results.  An  easily  foreseen  first  effect  is  a  reduction  in  blood  pressure. 
This  phenomenon  is  produced  as  soon  as  the  vein  is  open.  Tension 
rapidly  decreases,  to  again  rise  slowly  when  the  How  is  arrested,  and 
returns  to  a  figure  somewhat  below  that  observed  al  the  beginning. 
In  this  respect  successive  blood-lettings  act  less  and  less  enei  e 
cally.  Coincidently,  according  to  Marey's  law,  the  pulse  becomes 
more  rapid  and  weak.  If,  however,  arterial  tension  is  very  consid- 
erable and  venous  stasis  very  marked,  the  pulse  becomes  fuller.  The 
red  blood  corpuscles  diminish  in  number,  but  this  first  phenomenon 
is  followed  by  a  very  marked  increase  in  the  hematoblasts.  This 
second  result,  noted  by  Dr.  Hayem,  is  in  perfect  harmony  with  the 
researches  which  have  been  pursued  on  the  hematopoietic  organs, 
demonstrating  their  increased  functional  activity.  After  the  bleed- 
ing the  cells  proliferate  in  order  to  repair  the  losses  of  the  organism. 
and,  as  always,  compensation  exceeds  the  primary  effect.  The  slight 
leucocytosis  which  supervenes  in  most  cases  is  probably  produced 
by  the  same  mechanism.  The  diminution  of  the  blood  mass  has  two 
important  consequences:  it  facilitates  the  circulation  in  parts  which 
are  overloaded  with  blood  and  relieves  passive  congestions,  with  the 
result  that  the  functions  of  the  organs  are  better  fulfilled.  The  effect 
is  particularly  appreciable  in  the  lungs.  At  the  same  time,  an  osmotic 
current  is  established  from  the  tissues  toward  the  bloodvessels.  The 
interstitial  fluids  pass  into  the  circulation.  If  they  are  toxic,  their 
action  upon  the  organism  may  be  dreaded,  and.  in  fact.  Lisfranc 
rejected  blood-letting  whenever  a  purulent  or  putrid  focus  existed. 
If,  however,  elimination  is  easy,  blood-letting  favors  the  passage  into 


806  INFECTIOUS  DISEASES. 

the  blood  of  substances  deposited  in  the  interstitial  plasma,  and  thus 
promotes  disintoxication  of  the  organism.  Blood-letting  acts  the 
better  the  easier  the  work  of  the  heart  is  rendered  under  its  influence, 
and,  consequently,  the  urinary  secretion  is  increased.  As  a  matter 
of  fact,  experiments  have  demonstrated  that  diuresis  is  increased  in 
consequence- of  blood-letting.  Since  we  are  speaking  of  poisons,  it 
is  well  to  remark  that  blood-letting  is  one  of  the  best  means  for  freeing 
the  organism  from  them.  With  good  reason,  Prof.  Bouchard  has 
laid  stress  on  this  point.  He  notes  that  a  blood-letting  of  32  grams 
eliminates  from  the  organism  0.5  gram  of  extractive  matters. 
In  twenty-four  hours  the  urine  eliminates  8  grams  of  such  matters. 
Tli is  small  loss  of  blood  thus  throws  out  of  the  body  the  one-sixteenth 
part  of  the  poison  accumulating  in  one  day  when  urinary  secretion 
is  suspended.  This  result  seems  still  greater  when  it  is  remembered 
that  280  grams  of  intestinal  fluid  or  10  quarts  (9  litres)  of  sweat  are 
required  hi  order  to  produce  the  same  effect. 

By  modifying  blood  pressure,  blood-letting  is  followed  by  dilata- 
tion of  the  capillaries  and,  consequently,  a  more  active  irrigation  of 
the  tissues.  The  result  is  a  favorable  modification  in  nutrition.  In 
fact,  the  urine  of  twenty-four  hours  eliminates  more  urea,  more  phos- 
phoric acid  and  extractive  matters  (Lepine).  The  same  influence 
may  be  found  by  studying  the  organic  apparatus ;  the  nervous  system 
becomes  more  active,  and  respiration  easier  and  deeper.  A  last  effect 
of  blood-letting  is  a  modification  in  the  temperature.  Under  its  in- 
fluence temperature  is  lowered,  and  this  effect  is  the  more  marked  as 
calorification  is  increased.  The  thermometer  has  sometimes  marked 
one  or  two  degrees  less  after  blood-letting.  Unless,  however,  abun- 
dant and  repeated  bleedings  are  practised,  the  effect  is  transitory; 
the  temperature  soon  rises,  and  at  times  exceeds  the  former 
degree. 

Let  us  now  apply  these  data  to  infectious  diseases.  The  indica- 
tions may  be  formulated  in  the  following  manner:  Blood-letting  is 
indicated  for  combating  excessive  hyperthermia.  Congestion  in  the 
venous  system  embarrasses  cardiac  contraction  and  gives  rise  to 
passive  congestion  in  the  lungs,  kidneys,  and  brain.  The  result  is  a 
profound  and  rapid  intoxication  of  the  organism,  especially  if  renal 
insufficiency  coexists. 

Blood-letting  is  contraindicated,  even  under  the  foregoing  condi- 
tions, in  children,  the  aged,  and  debilitated  individuals.  In  other 
words,  the  advisability  of  blood-letting  is  to  be  considered  only  as 


THERAPEUTICS  OF  TNFE0TI0U8  DISEASES.  807 

regards  vigorous  adults,  especially  tho  epre  enting  whal  the  ancient* 
designated  under  the  terra  plethoric  temperament. 

Let  us  now  consider  a  determined  infection,  the  only  one,  perl 
in  which  blood-letting  is  still  quite  frequently  employed  i.e., 
pneumonia.  formerly,  blood-letting  wa  resorted  to  j  tematically. 
Tommasini,  of  Bologne,  practised  ;is  many  as  twenty  blood-lettings 
of  from  loo  grams  to  500  grams  each.  He  thus  drew  ten  quarU 
(nine  litres)  of  Mood.  Broussais  and  Bouillaud  followed  an  analo- 
gous method.  Ai  presenl  there  is  general  agreemenl  thai  blood- 
letting  does  not  check  pneumonia  :  ii  does  not  even  abridge  its  course, 
Out,  it,  improves  certain  symptoms.  It  is  indicated  in  all  vigi 
adults  in  whom  lexer  is  intense  and  dyspnea  is  troublesome  and  in 
whom  an  extensive  focus  surrounded  by  ;i  vasl  zone  of  hyperemia 
and  edema  is  found.  It  is  likewise  indicated  when  the  patienl  i- 
cyanosed  and  (lie  righl  hear!  is  dilated;  also  when  venous  stasis 

affects  (lie  bruin,  giving  rise  to  somnolence  or  ;i  semicomatose  state. 
Iii  this  case,  blood-letting  brings  immediate  relief;  respiration  be- 
comes freer,  deeper,  and  shorter;  the  pulse  is  strengthened,  the  ner- 
vous disturbances  diminish,  and  in  several  cases  an  amelioration  in 
cardiac  manifestations  and  increased  diuresis  are  clearly  observed. 

Blood-letting  has  been  practised  in  all  infectious  diseases.  Typhoid 
fever,  eruptive  fevers,  erysipelas,  inflammations  of  the  serous  mem- 
branes, and  especially  acute  articular  rheumatism  have  been  treated 
by  blood-letting.  Dr.  Du  Castel  thinks  that  this  method  may  render 
service  in  variola  when  very  marked  phenomena  of  cerebral  stasis 
are  present.  This  particular  case  excepted,  blood-letting  is  indicate.  I 
in  infectious  diseases  when  intense  pulmonary  and  renal  disturbances 
are  observed.  It  may  likewise  be  available  in  other  localizations  in 
the  viscera  or  serous  membranes.  In  this  case,  however,  local  deple- 
tions and  wet  cuppings  are  mostly  employed. 

Blood-letting  is,  therefore,  reserved  for  those  cases  in  which 
intense  pulmonary  congestion  hinders  hematosis  and  embarrass  - 
the  function  of  the  right  heart.  It  becomes  altogether  urgent  in 
cases  of  acute  pulmonary  edema.  In  certain  fever  cases,  especially 
when  renal  lesions  are  present,  pulmonary  edema  may  rapidly 
appear  and,  at  times,  cause  death  within  a  few  minutes.  This 
dangerous  manifestation  is  observed  particularly  during  convales- 
cence in  the  course  of  scarlatinal  nephritis.  This  is  one  of  the  most 
formal  indications  for  blood-letting,  as  the  procedure  gives  mar- 
vellous results  against  this  visceral  manifestation. 


808  INFECTIOUS  DISEASES. 

When  the  renal  lesion  influences  the  nervous  system  the  indication 
for  blood-letting  is  not  any  less  clear.  It  is  likewise  during  con- 
valescence from  scarlatina  that  uremic  accidents  involving  the  brain 
are  observed  and  command  bleeding.  While  this  method  is  service- 
able against  the  symptoms  of  chronic  nephritis,  it  is  particularly 
indicated  in  acute  nephrites  which  manifest  a  natural  tendency 
toward  recovery.  It  suffices  to  assist  the  organism  a  little  in  order 
to  avoid  grave  manifestations. 

The  knowledge  of  the  role  played  by  intoxication  in  the  production 
of  infectious  symptoms  leads  to  the  question  whether  it  would  not 
be  advisable  to  practise  blood-letting  in  certain  grave  cases.  The 
amount  of  poisons  impregnating  the  economy  would  thus  be  dimin- 
ished. The  suggestion  is  evidently  rational.  It  may,  however,  be 
objected  that  the  loss  of  blood  would  weaken  the  patient.  The 
question  is  again  laid  before  us  to-day.  We  know,  in  fact,  the 
marvellous  results  of  salt-water  injections  in  the  treatment  of  infec- 
tions. Some  authorities  have,  therefore,  proposed  to  combine  the 
two  methods.  The  idea  is  perfectly  reasonable,  and  the  disadvantages 
of  venesection  are  thus  offset  by  saline  infusion. 

Injections  of  Artificial  Serum. 

Intravenous  or  subcutaneous  injections  of  artificial  serum  are 
daily  employed  at  present  in  the  treatment  of  the  most  varied 
infections.  While  there  is  general  agreement  as  to  their  usefulness, 
their  mode  of  action  is  still  a  subject  of  controversy.  Drs.  Dastre 
and  Loye,  who  were  the  first  to  transfer  the  question  to  experimental 
ground,  suppose  that  salt-water  injections  realize  lavage  of  the 
organism.  It  has  been  objected,  however,  that  in  hydremic  animals 
the  renal  secretion  is  profoundly  modified.  The  urine  is  an  aqueous 
fluid  which,  in  certain  cases,  carried  less  extractive  matters  than  it 
would  under  normal  conditions.  Some  experimental  investigations 
have  confirmed  this  conclusion  by  demonstrating  that  infected  or 
intoxicated  animals  upon  which  lavage  of  the  blood  is  practised  die 
before  the  controls.  It  is  to  be  noted  that  the  problem  is  far  more 
complex  than  seems  at  first  view.  When  salt-water  is  injected 
beneath  the  skin  or  into  the  veins  quite  different  effects  are  pro- 
duced. The  amount  of  fluid  contained  in  the  vessels  is  modified. 
Contrary  to  what  might  be  expected,  the  blood  pressure  varies 
little,  at  least  if  it  was  normal.  We  must,  therefore,  presume  that 
either  vasomotor  modifications  or  some  eliminations  have  rapidly 


THERAPEUTICS  OF  INFECTIOUS  DISEA8E8.  809 

taken  place.  In  the  latter  instance,  if  a  portion  of  the  fluid  i 
jected  by  the  emunctories,  another  portion  i  deposited  in  certain 
tissues,  and  modifies  the  nutrition  of  the  organ]  en,  and  con  equently 
produces  changes  in  the  activity  of  vrariou  pari  .  A  a  thattei  of 
fact,  experiments  have  demonstrated  thai  the  responsive  aptitude 
of  the  nervous  system  is  considerably  increased.  Thie  modification 
is  immediate;  it  supervenes  immediately  after  the  injection.  A.1 
the  same  time,  however,  the  nutritional  modification*  are  foil 
by  changes  in  the  histological  structure  of  certain  tissues.  Thifi 
is  readily  recognized  by  studying  the  bone-marrow. 

Influence  of  Injections  of  Artificial  Serum  upon  Absorption.  The 
first  question  is  whether  injections  of  salt-water  modify  the  absorp- 
tion of  poisons  deposited  beneath  the  skin  or  in  the  alimentary 
canal.  Magendie  took  up  this  problem.  He  introduced  a  poison 
into  the  pleura  after  having  practised  blood-letting.  The  disturb- 
ances were  manifest  at  the  end  of  thirty  seconds,  while  in  an  intacl 
animal  they  did  not  appear  until  two  minutes  after.  On  the  other 
hand,  when  he  injected  one  or  two  quarts  (litres)  of  water  into  the 
veins  the  symptoms  were  then  inure  tardy;  they  often  did  not  appear 
when  two  quarts  were  introduced.  When,  however,  blood-letting 
was  practised  upon  this  hydremic  animal  the  toxic  manifestations 
developed  as  the  blood  was  flowing.  The  experiments  of  Delbet 
likewise  established  that  intravenous  injections  of  salt  water  prevent 
the  absorption  of  strychnine  introduced  into  the  peritoneum.  More 
recent  experiments  pursued  by  Dr.  Ghassevant  also  demonstrated 
that  such  injections  retard  and  attenuate  the  action  of  strychnine 
introduced  beneath  the  skin.  Taking  up  this  question,  I  learned 
that  salt-water  effectively  retards  the  absorption  of  strychnine. 
The  fluid  was  injected  into  rabbits  by  the  intravenous  route,  at  a 
temperature  of  102.2°  F.  (39°  C),  in  amounts  of  3  to  4  c.cm.  per 
minute  per  kilogram  of  animal.  The  amount  introduced  varied 
from  3  to  228  c.cm.  per  kilogram.  Five  minutes  after  the  salt- 
water injection  the  animals  received  subcutaneously  from  I  I 
mg.  of  strychnine  sulphate.  The  injections  of  salt-water  in  doses 
of  3  to  70  c.cm.  per  kilogram  did  not  greatly  modify  the  resistance 
of  the  animals;  at  times  they  increased  it.  and  at  other  times  they 
diminished  it.  "When,  however,  considerable  quantities  were  intro- 
duced, that  is  from  166  to  228  c.cm.  per  kilogram,  the  symptoms 
were  delayed  and  less  marked.  Thus.  1  mg.  killed  a  rabbit  within 
eighteen  to  thirty-one  minutes:  while  it  takes  half  an  hour  to  kill 


810  IXFECTIO  US  DISEA  SES. 

an  animal  having  previously  received  210  c.cni.  of  salt-water  per 
kilogram.  By  diminishing  the  dose  of  the  poison  we  observed  no 
disorder  whatever.  In  one  rabbit  7  mg.  produced  no  disturbance, 
not  even  an  exaggeration  of  the  reflexes,  while  two  other  rabbits 
which  received  the  same1  amount  of  strychnine  per  kilogram,  had 
intermittent  convulsions  extending  over  a  period  of  seven  or  eight 
minutes;  then  the  animals  recovered,  although  for  thirty  to  forty 
minutes  they  retained  a  very  marked  exaggeration  of  the  reflexes. 

When  strychnine  is  injected  into  the  veins  instead  of  beneath 
the  skin,  the  results  are  different.  The  animals  which  received  salt- 
water reacted  far  more  rapidly  and  energetically,  and  died  before 
the  controls.  This  result  demonstrates  that  injections  of  salt-water, 
while  retarding  the  action  of  strychnine  injected  beneath  the  skin, 
do  not  act  by  diminishing  the  sensibility  of  the  animals.  It  must, 
therefore,  be  admitted  either  that  they  hasten  elimination  or  that 
they  hinder  absorption.  By  injecting  strychnine  into  the  veins  at 
a  very  slow  rate,  so  as  to  introduce  the  convulsifying  dose  in  an 
hour  and  a  half,  elimination  should  be  effected  still  more  easily 
than  is  the  case  in  subcutaneous  injections.  The  animals  should 
not  present  any  disorder.  Experiments  having  given  the  contrary 
result,  I  concluded  that  the  role  of  elimination  is  insignificant. 
Injection  of  large  quantities  of  salt-water  into  the  veins  retard  and 
diminish  strychnine  intoxication  because  they  hinder  absorption. 

Here,  therefore,  is  a  first  result  which  must  be  taken  into  account 
for  therapeutic  indications.  The  result  should  not,  however,  be 
generalized.  What  is  true  of  alkaloids  is  not  applicable  to  microbic 
toxins.  Enriquez  and  Hallion  demonstrated  that  previous  injections 
of  salt-water  in  nowise  prevent  the  absorption  of  diphtheritic  toxins 
injected  beneath  the  skin. 

Influence  of  Injections  of  Artificial  Serum  upon  Elimination. 
What  is  the  influence  of  intravenous  injections  upon  renal  elimina- 
tion? Numerous  researches  have  been  pursued  on  this  subject. 
Dastre  and  Loye,  who  have  well  studied  the  method  from  an  experi- 
mental standpoint,  practised  lavage  of  the  blood.  The  attempts, 
however,  which  were  made  to  save  the  intoxicated  or  infected 
animals  generally  gave  no  results.  The  animals  thus  treated  died 
more  rapidly  than  the  controls.  By  studying  the  urine  of  animals 
having  received  such  amounts  of  salt-water  as  to  double  the  blood 
mass,  Carrion  and  Hallion  learned  that  while  the  amount  of  water 
excreted  increases,  the  amount  of  matters  eliminated,  except  that  of 


THERAPEUTICS  OF  TNFE0TI0U8  diseases.  nil 

sodium  chloride,  is  mailer  than  normal.  Sodium  chloride  i  substi- 
tuted in  the  mine  for  other  materials)  il  doe  nol  carry  them  away. 
These  results  account  for  the  failure  of  attempt*  ol  experimental 
therapeutics. 

These  results,  however,  should  no1  !"•  ha  Hi',  generalized. 
matter  of  fact,  I  have  obtained  differenl  result*   by  studying  the 
elimination  of  two  substances  which  are  ea  il)  detected  in  the  urine 
— ferrocyanide  of  potassium  and  Bulphindigotate  of  soda. 

In  a  first  series  of  experiments,  rabbits  received  through  a  vein 
of  the  ear  I  c.cm.  of  a  1 :  20(  I  solution  (2  centigrams)  of  ferro- 
cyanide of  potassium.  The  injection  lasted  a  minute.  Then  an 
effort  was  made  to  discover  al  what  moment  the  urine  gave  the 
characteristic  blue  color  with  perchloride  of  iron.  In  order  to  deter- 
mine this,  we  collected  every  minute  a  few  drop-  of  the  urine  either 
by  means  of  ;i  catheter  or  by  compressing  the  bladder  through  the 
abdominal  wall.  By  experimenting  upon  sis  normal  rabbits  we 
discovered  the  presence  of  ferrocyanide  in  the  urine  ;it  the  end  of 
ten,  eleven,  thirteen,  fourteen,  sixteen,  and  seventeen  minutes 
thirteen  minutes  on  an  average.  In  lour  rabbits  into  which  we 
injected  salt-water  before  the  introduction  of  the  ferrocyanide  we 
obtained  the  following  figures:  seven  minutes  in  a  first  rabbit 
having  previously  received  62  c.cm.  of  salt-water  per  kilogram;  -i\ 
minutes  in  a  second  rabbit  having  received  100  c.cm.:  eight  minutes 
in  two  others,  one  having  received  133  and  the  other  160  con.  per 
kilogram:  the  average  is  seven  minutes.  The  differences  are.  there- 
fore, very  clear.  The  previous  injection  of  salt-water  caused  the 
ferrocyanide  to  appear  in  the  urine  twice  as  rapidly  as  in  the  controls. 

It  is  very  difficult  to  determine  at  the  end  of  what  time  elimination 
is  completed,  for  the  ferrocyanide  diminishes  little  by  little,  and  a 
moment  arrives  when  reaction  with  perchloride  of  iron  becomes 
extremely  doubtful.  Nevertheless,  here  are  figures  presenting  a 
comparative  value.  In  three  normal  rabbits  reaction  discontinued 
respectively  at  the  end  of  tour  hours,  four  hours  and  forty  minutes, 
and  five  hours.  In  three  rabbits  which  received  salt-water  after  the 
injection  of  the  ferrocyanide  reaction  ceased:  in  the  first  one.  which 
had  received  62  c.cm.  per  kilogram,  at  the  end  of  four  hours:  in 
the  other  two,  which  had  received  each  100  c.cm.  at  the  end  of 
three  hours  and  forty  minutes  and  three  hours  and  thirty  minutes, 
respectively.  Thus,  it  may  be  stated  that,  on  an  average,  elimina- 
tion lasts  four  hours  and  thirty-three  minute?  in  the  controls,  and 


812  INFECTIOUS  DISEASES. 

three  hours  and  forty-three  minutes  in  the  injected  animals.  The 
differences  are  appreciable,  but  not  important. 

Clearer  results  may  be  obtained  by  the  employment  of  sulphindi- 
gotate  of  sodium.  When  2  c.cm.  of  a  3  per  cent,  solution  of  this 
substance  is  injected  into  the  veins  of  a  rabbit,  at  the  end  of  three 
or  four  minutes  a  urine  of  a  decidedly  blue  color  begins  to  flow. 
The  passage  of  the  coloring  substance  is,  therefore,  effected  far  too 
rapidly  to  permit  the  experimenter  to  notice  differences  in  hydremic 
animals.  Hence,  I  simply  sought  to  learn  whether,  by  injecting 
salt-water  after  the  introduction  of  indigo,  I  favored  the  elimination 
of  this  coloring  matter.  The  results  were  similar  to  those  obtained 
with  ferrocyanide :  the  urine  recovered  its  normal  aspect  at  the  end 
of  four  hours  and  a  half  in  the  controls,  and  at  the  end  of  three 
hours  and  a  half  to  three  hours  and  fifteen  minutes  in  the  treated 
animals.  It  is  understood  that  in  all  these  experiments  the  varying 
degrees  of  dilution  of  the  excreted  fluid  were  always  taken  into 
account. 

In  order  to  obtain  a  more  convincing  demonstration  of  the  influ- 
ence exercised  by  injections  of  salt-water,  I  introduced  into  the 
veins  15  to  20  c.cm.  per  kilogram  of  a  3  per  cent,  solution  of  sulphin- 
digotate  of  soda.  The  animals  soon  presented  a  bluish  color,  fairly 
appreciable  in  the  nose,  lips,  gums,  nictitating  membrane,  and  con- 
junctiva. On  cutting  off  the  fur  the  skin  was  found  to  be  of  a 
deep  blue  color.  Preserving  one  animal  as  control,  I  injected  salt- 
water into  the  other.  An  injection  of  130  c.cm.  per  kilogram 
notably  accelerated  the  return  of  the  normal  color,  especially  in  the 
mucous  membranes.  At  the  end  of  an  hour  and  a  half,  for  example, 
the  buccal,  nasal,  and  ocular  mucous  membranes  became  grayish; 
at  the  end  of  two  hours  or  two  hours  and  a  half  they  recovered 
their  normal  hue.  At  this  moment,  in  the  control  animals  the 
same  parts  were  still  of  a  slightly  greenish-blue.  The  differences 
were  analogous  with  regard  to  the  skin,  but  they  were  less  marked. 
With  the  controls  as  well  as  with  the  treated  animals,  decolorization 
was  effected  far  more  slowly  in  the  skin  than  in  the  mucous  mem- 
branes. The  results  were  the  same  in  the  viscera.  On  sacrificing 
the  animals  at  different  moments  I  noticed  that  decolorization 
was  more  rapidly  produced  in  those  which  had  received  salt-water 
injections.  For  example,  at  the  end  of  three  hours  the  liver  had 
resumed  its  normal  aspect,  while  it  was  still  blue  in  the  controls. 
The  kidneys  remained  colored  for  a  longer  time,  but  their  color 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  .-].". 

was  less  marked.  Lastly,  a1  the  end  of  seven  bom  .  the  .1  nim.-i I- 
treated  presented  very  little,  if  any,  abnormal  color;  while  the 
kidneys  and  the  tendons  of  the  controls  were  still  blue. 

[t  may,  therefore,  be  concluded  thai  intravenous  injection 
salt-water  truly  realize  lavage  of  the  Mood  or  rather  of  the  organism ; 
they  hasten  the  appearance  of  ferrocyanide  of  potassium  in  the 
urine  and  accelerate  its  elimination.  Finally,  as  our  experiment* 
with  indigo  demonstrated,  they  promote  elimination  of  noxious  sub- 
stances deposited  in   the  tissues. 

It  would  be  worth  while  to  take  up  the  study  of  the  question  I  y 
varying  the  doses  and  employing  the  mosl  varied  substances.  I< 
would  thus  be  possible  lo  establish  the  laws  of  elimination.  All 
that  we  can  say  a1  present  is  thai  injections  of  artificial  serum  seem 
to  produce  divers  effects  according  to  the  substances  employed. 
They  favor  elimination  of  some  and  hinder  thai  of  others. 

Influence  of  Injections  of  Artificial  Serum  upon  the  Functions 
and  Nutrition  of  the  Organism.  The  study  of  strychnine  intoxica- 
tion enabled  me  to  recognize  thai  injections  of  artificial  serum 
modified  the  responsive  aptitudes  of  the  organism.  In  order  to 
avoid  errors  arising  from  modifications  in  absorption,  it  is  necessary 
to  introduce  the  poison  directly  into  the  veins.  The  results  were 
extremely  clear.  By  injecting  into  the  veins  doses  of  strychnine 
which  produced  no  disturbance  in  the  controls,  I  caused  fatal  con- 
vulsions in  the  hydremic  animals.  In  several  of  my  experiments 
the  injections  were  made  very  slowly.  I  thus  hoped  to  allow  time 
for  renal  elimination  to  take  place;  but  no  matter  whether  the  rate 
of  the  injections  was  rapid  or  slow,  the  result  was  the  same.  The 
conclusion  is,  therefore,  that  salt-water  injections  increased  reflex 
excitability;  the  employment  of  strychnine  was  designed  to  deter- 
mine the  sensibility  of  the  spinal  cord.  The  concordant  results 
obtained  demonstrate  that  saline  infusion  produces  a  dynamogeny 
in  the  nervous  centres.  This  therapeutic  method  is.  therefore, 
indicated  in  all  cases  of  depression  or  asthenia.  Clinical  experience 
shows  that  this  deduction  is  well  founded. 

Another  point  on  which  clinical  observation  and  experimentation 
are  agreed  is  the  influence  exercised  upon  the  blood  pressure.  In 
certain  cases  pressure  rises  by  a  very  simple  mechanism.  For 
example,  in  the  ease  of  an  individual  in  whom  the  arterial  pulsation 
is  no  longer  appreciable,  and  death  seems  to  be  imminent  as  the 
result  of  profuse  hemorrhage,  injection  of  salt-water  into  the  veins 


814  ISFECTIOUS  DISEASES. 

revives  the  patient  immediately;  the  cardiac  pulsations  are  strength- 
ened, and  the  pulse  improves.  On  the  other  hand,  it  may  be  sup- 
posed that  the  injections  also  act  upon  the  nervous  centres  and 
that  they  indirectly  raise  blood  pressure.  This  action  may  account 
tnr  the  results  obtained  in  the  treatment  of  infections  of  the  digest  ive 
canal,  such  as  cholera,  enteritis,  and  infections  of  the  peritoneum. 
It  is  precisely  in  such  cases  that  the  blood  pressure  falls  to  the 
minimum.  Bosc  and  Yedel  demonstrated  the  good  results  of  saline 
injections  in  animals  which  were  inoculated  with  the  colon  bacillus. 
On  the  other  hand,  Enriquez  and  Hallion  followed  the  variations 
of  blood  pressure  in  animals  at  the  last  stage  of  diphtheritic  intox- 
ication. Under  the  influence  of  the  injections  the  blood  pressure, 
which  had  been  very  low,  was  seen  to  rise  progressively,  while  the 
various  symptoms  improved.  Amelioration  was  not,  however, 
permanent.  This  was  probably  due  to  the  fact  that  experimental 
intoxication  was  too  brutal,  and  the  animals  could  not  be  saved. 

The  nervous  and  circulatory  functions  as  well  as  all  the  tissues 
of  the  organism  are  favorably  influenced  by  injections  of  salt-water. 
L.  Gamier  and  Lambert  demonstrated  that  the  muscles  consumed 
more  oxygen  and  eliminated  more  carbonic  acid.  This  modification 
seems  to  be  quite  independent  of  any  nervous  influence,  since  it 
was  observed  in  the  muscles  separated  from  the  body  of  the  animal. 
The  same  authors  have  likewise  discovered  that  the  amount  of 
glycogen  diminished  in  the  liver,  not  because  it  was  eliminated,  but 
simply  because  the  hepatic  cells  had  become  more  active  and  con- 
sumed it  more  rapidly.  Chemical  analysis  thus  agrees  with  experi- 
mentation and  clinical  observation  to  establish  that  artificial  serum 
is  a  powerful  stimulant  of  nutritional  activity  and  that  it  possesses 
a  high  dynamogenic  power.  Histological  investigations  prove  the 
same  thing.  To  be  convinced  of  this,  it  suffices  to  examine  the 
bone-marrow  of  animals  submitted  to  this  medication.  I  recognized, 
with  Dr.  Josue,  that  fat  was  rapidly  absorbed  and  the  cells  of  the 
marrow  proliferated.  This  fact  presents  certain  interest  from  the 
standpoint  of  pathological  physiology,  since  it  is  known  that  bone- 
marrow,  by  furnishing  round  cells  to  the  blood,  plays  an  important 
role  in  the  defense  of  the  organism  against  infections. 

Indications  of  Injections  of  Artificial  Serum.  The  first  attempts 
were  made  as  early  as  1831.  Joeniken,  of  Moscow,  injected  slightly 
acidulated  water  into  a  cholera  patient  at  the  point  of  death.  The 
patient  died  two  hours  later.     A  Scotch  physician,  Latta,  in  1832, 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  -\., 

advocated  intravenous  injection*  of  all  water  in  cholera.  In  1850 
Zimmermann  treated  by  thie  method  a  certain  numbei  of  cholera 
patients,  and  reported  thirty  cure  Lorain,  in  1866,  and  Dujardin- 
Beaumetz,  in  L876,  reported  other  facl  .  The  e  fii  I  attempt*  did 
not,  however,  have  follower  ,  and  we  musl  turn  to  the  contributions 
oJ  Hayem  to  see  intravenous  injection  or  artificial  erum  take  - » r  t 
importanl  place  in  i  herapeul  ic  . 

Subcutaneous  or  intravenous  injections  of  jail  water  are  al  pre 
employed  in   the  treatmenl   of  the  mosl   varied  infections.     The 
quality  of  fluid  to  be  injected  has  been  varied.    On  the  ba 
highly  interesting  theoretical  considerations,  Quinton   has  recently 
proposed  to  employ  diluted  sea-water.    This  liquid  U  .— - » i *  1  to  be 
better  borne  and  to  exercise  a  more  energetic  therapeutic  action. 

In  our  wards  we  employ  either  8 per  1000  solutions  ol  aalt-water 
or  Hayem's  serum,  which,  as  is  known,  contains  5  grams  of  Na<  'I  and 
10  grams  of  Na2S04  per  litre  (quart).  Hie  liquid  i-  Bterilized  and 
introduced  after  being  heated  to  104°  F.  C4()°  ('.).  Dawborn  fin- 
ployed  solutions  heated  to  120.2°  V.  I  I*.)  C).  While  the  experi- 
ments of  Riehet,  Langlois,  and  Atlianasiu  demonstrated  that  injec- 
tions of  hot  water  are  well  borne  by  animals,  those  of  Lepine  and 
ours  show,  on  the  other  hand,  that  ice-water  does  not  produce  any 
disturbance.  It  may  be  concluded  that  the  body  heat  may  be 
modified  by  injections  of  more  or  less  heated  fluids.  For  the  time 
being,  it  seems  more  prudent  to  employ  solutions  the  temperature 
of  which  is  near  that  of  the  body.  This  precaution  is  indispensable 
when  an  intravenous  injection  is  practised.  It  is  less  important  in 
subcutaneous  injections.  When  it  is  necessary  to  act  promptly, 
intravenous  injection  is  preferable.  If.  however,  the  vein  cannot 
be  discovered,  for  example,  in  an  obese  individual  or  in  a  patient 
whose  bloodvessels  have  contracted,  intraperitoneal  injection  may 
be  practised.  According  to  experiments  pursued  on  animals,  this 
method  is  harmless  and  has  the  advantage  of  permitting  very  rapid 
absorption.  When  there  is  no  urgency  the  fluid  may  be  in;- 
into  the  rectum,  after  having  given  an  evacuative  enema. 

Whatever  the  route  of  introduction,  injections  produce  identical 
effects,  appreciable  especially  in  the  cast1  oi  intravenous  injections. 
Bosc,  Vedel,  and  Michaux  have  described  the  various  manifestations 
observed  under  these  circumstances.  During  the  injection,  the 
pulse  becomes  slower,  more  regular  and  stronger.  The  central  and 
axillary  temperatures  slightly  rise:  sometimes  diarrhea  is  produced. 


816  IXFECTIO  US  DISEASES. 

Immediately  after  the  injection,  the  patient  experiences  a  feeling 
of  quiet  exhilaration  which  lasts  from  thirty  minutes  to  an  hour. 
Then  violent  chills  supervene ;  the  extremities  become  cold  and  blue ; 
the  pulse  and  respiration  are  accelerated,  and  the  reflexes  exagger- 
ated. The  temperature  rapidly  rises.  The  patient  then  experiences 
a  sensation  of  heat.  This  second  stage  is  followed  by  a  more  or 
less  rapid  return  to  the  normal.  In  certain  instances  fever  dis- 
appears completely  and  in  a  definitive  manner.  Owing  to  the  violent 
reaction  thus  produced,  the  organism  seems  to  have  arrested  the 
morbid  evolution. 

After  subcutaneous  injections  similar  reactions  occur,  but  they 
are  more  tardy  and  less  intense.  Intravenous  injection  is  indicated 
particularly  in  very  acute  infections  and  in  diseases  aggravated  by 
a  sudden  complication.  Cholera  and  choleriform  diarrheas  belong 
to  the  first  instance;  peritoneal  infections,  supervening  in  conse- 
quence of  a  surgical  operation  or  in  the  course  of  an  infection,  may 
likewise  be  treated  b}^  this  method.  In  cases  of  peritonitis,  a  reduc- 
tion in  arterial  pressure  is  not  infrequently  the  first  symptom 
observed.  An  intravenous  injection  raises  the  blood  pressure,  and 
thereby  stimulates  activity  of  the  glands  and  assures  diuresis.  The 
results  of  intravenous  injections  are  often,  however,  of  a  transitory 
character.  It  is  then  necessary  to  repeat  the  injection  of  the  fluid. 
If  one  litre  is  injected,  four  or  five  similar  injections  may  be  given 
in  twenty-four  hours.  In  one  case  Lejars  introduced  seven  litres 
in  seven  hours.  In  another  instance  he  injected  twenty-six  litres 
in  nine  days. 

Very  satisfactory  results  may  also  be  obtained  by  combining 
subcutaneous  and  intravenous  injections.  Owing  to  their  immediate, 
almost  instantaneous,  effects  the  latter  palliate  the  early  symptoms. 
The  introduction  of  salt-water  beneath  the  skin  furnishes  to  the 
economy  a  provision  of  fluid  which  passes  slowly  into  the  blood  as 
the  emunctories  eliminate  the  water  introduced.  In  infections  with 
a  slow  course,  in  adynamic  fevers,  and  in  cases  of  myocarditis 
subcutaneous  injections  are  usually  employed.  Finally,  when  a 
profound  intoxication  of  the  organism  is  suspected,  blood-letting  and 
transfusion  may  be  combined.  Everyone  knows  of  this  method 
proposed  by  Dr.  Barre:  150  to  300  c.cm.  of  blood  are  taken  from 
a  vein,  and  from  200  to  1200  c.cm.  of  salt-water  are  then  injected 
into  the  veins  or  beneath  the  skin. 

The  amount  of  the  fluid  injected  varies  considerably  according  to 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  -17 

the  individual  under  treatment,  the  di  ea  e  ob  erved,  and  th< 
pursued.    In  grave  cases,  from  600  c.cm.  to  1000  c.cm.  ol  artificial 
serum  are  introduced  into  the  veins.     In  mo  I  ca  e    the  author 
employs  subcutaneous  injections.    The  amount  varies  accordii 
the  age  of  the  subjecl  and  the  nature  and  gravity  of  the  ca  e.    En 
children  about  two  years  of  age,  from  10  c.cm.  to  20  c.cm.  suffice. 
The  author  generally  injects  from  200  c.cm.  to  300  ccm.  in  the 
of  adults.    II  the  case  is  more  seriou  .  from  MX)  c.cm.  to  500  ccm. 
may  be  used.    Moreover,  in  case  of  need,  subcutaneous  injections 
may  be  repeated  several  limes  a  day,  and  it  is  surprising  to  see  with 
what  facility  patients  bear  them. 

All  sorts  of  infections  may  be  treated  by  this  method.  It  is 
employed  in  all  grave  pyrexias,  notably  in  those  in  which  the  nervous 
system  is  extremely  weakened  and  there  is  tendency  to  adynamia 
and  cardiac  collapse,  a  dehydration  of  the  organism  expressed  by  the 
dryness  of  the  mucous  membranes  and  of  the  skin,  a  diminution  in 
the  amount  of  urine,  and  the  occurrence  of  profuse  and  multiple 
hemorrhages. 

The  existence  of  pulmonary,  renal,  or  cardiac  complication-  i-  at 
times  considered  a  contraindication.  Lesions  of  the  lungs,  the  author 
thinks,  contraindicate  intravenous  injections,  hut  they  should  in  no- 
wise prevent  subcutaneous  injections.  He  often  prescribes  artificial 
serum  for  children  suffering  from  bronchopneumonia,  provided,  how- 
ever, that  small  amounts  be  given  two  or  three  times  a  day.  The 
same  rule  should  be  followed  in  the  case  of  renal  or  cardiac  compli- 
cations. Experience  has  demonstrated  that  intravenous  injections 
are  often  harmful,  and  if  a  lesion  of  the  heart  is  present,  this  may 
cause  sudden  death.  On  the  contrary,  subcutaneous  injections  are 
well  borne.  The  method  is  available  not  only  during  the  stationary 
period,  but  at  the  end  and  during  convalescence  from  infections. 
The  author  has  resorted  to  it  several  times  when  recovery  was  not 
clearly  established,  notably  at  the  end  of  typhoid  fever.  An  injec- 
tion of  100  c.cm.  often  suffices  to  cause  the  last  symptoms  to  d> 
pear.  During  convalescence  from  infections,  when  the  patient  is  not 
restored  to  health  with  gratifying  rapidity,  recourse  may  be  had  to 
injections  of  small  amounts  of  saline  solutions,  following  the  advice 
of  Landouzy.  From  10  c.cm.  to  20  c.cm.  of  artificial  serum  are 
introduced  beneath  the  skin  twice  a  week.  This  is  a  method  which 
renders  most  appreciable  service  in  the  case  of  tedious  convales- 
cence. 


818  IXFECTIOUS  DISEASES. 

Special  Indications  for  Injections  of  Artificial  Serum.  After  the  gen- 
eral study  which  we  have  presented  concerning  saline  injections,  we 
shall  be  very  brief  on  particular  indications. 

Numerous  cases  of  surgical,  obstetrical,  and  medical  septicemias 
have  been  successfully  treated  by  this  method.  Intravenous  injec- 
tions have  mostly  been  employed.  Turner  reported  two  cases  of 
tetanus  cured  by  saline  injections  preceded  by  blood-letting.  The 
attempts  made1  in  hydrophobia  by  Magendie,  Ore,  and  Reclus  were 
negative.  Among  medical  affections,  digestive  infections  particu- 
larly are  best  treated  by  this  method.  Cholera  is  the  disease  which 
is  most  frequently  treated  by  intravenous  injections.  In  order  to 
succeed,  it  is  necessary,  as  has  been  shown  by  Hayem,  to  intervene 
early,  as  soon  as  the  pulse  shows  weakness,  and  not,  as  is  often  done, 
in  the  period  of  collapse.  From  1500  c.cm.  to  2000  c.cm.  and  even 
2500  c.cm.  are  injected  into  the  veins.  If  the  symptoms  return,  the 
injection  is  repeated  on  the  following  day.  In  certain  instances 
recovery  has  been  obtained  only  after  five  or  six  intravenous  injec- 
tions. As  has  already  been  stated,  there  is  advantage  in  injecting 
at  the  same  time  400  c.cm.  to  500  c.cm.  beneath  the  skin.  In  mild 
cases  the  subcutaneous  method  exclusively  is  used.  Finally,  excel- 
lent results  are  obtained  b}^  prescribing  coincidently  warm  baths  so 
as  to  maintain  the  temperature  of  the  body  and  avoid  return  of  the 
algid  state.  The  same  rules  are  applicable  to  choleriform  ententes. 
The  indications  are  the  same;  the  less  grave  the  symptoms  the  more 
sufficient  the  hypodermic  method  generally  proves  to  be.  Treatment 
is  likewise  identical  in  cases  of  gastroenterites  of  the  newborn  and 
cholera  infantum.  Marfan  advises,  with  good  reason,  the  addition 
of  a  small  amount  of  caff ein  to  the  fluid :  75  eg.  of  citrate  or  benzoate 
of  caffein  are  added  to  300  c.cm.  of  salt-water,  and  three  injections 
of  5  c.cm.  to  20  c.cm.  daily  are  given. 

Typhoid  fever,  especially  its  adynamic  forms,  is  favorably  influ- 
enced by  the  injections.  In  the  case  of  intestinal  hemorrhage,  the 
effects  of  the  injections  are  very  remarkable.  In  order  to  be  con- 
vinced of  this,  it  suffices  to  bleed  an  animal.  At  the  moment  at 
which  death  seems  to  be  imminent  an  intravenous  injection  is  prac- 
tised, and  immediately  the  heart  beats  with  energy  and  all  the  dis- 
turbances disappear.  In  mild  cases  saline  injection  beneath  the  skin, 
and,  if  the  symptoms  are  alarming,  into  the  veins,  is  the  preferable 
treatment.  By  this  method  patients  who  had  already  fallen  into  a 
state  of  collapse  have  been  cured.    The  second  important  complica- 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  819 

tion  i.  c,  perforation  of  the  inte  tine  lik<  ri  e  require  b  saline 
injection,  which  renews  the  forces  of  the  patienl  and  enables  him  to 
bear  surgical  intervenl  ion. 

Among  other  infection  .  typhus  fever,  typhoidal  affections .  notably 
ulcerating  endocarditis  and  adynamic  pneumonia,  musl  ix 
by  subcutaneous  injections.  The  author  employs  them  also  in  erup- 
tive fevers,  at  leasl  in  grave  forms,  and  in  erysipelas.  When  the 
manifestations  persisl  and  the  temperature  remains  high  in  Bpite  of 
cold  baths,  subcutaneous  injection  often  i  unices  to  bring  aboul 
defervescence.  In  several  cases,  after  having  introduced  300  c.cm. 
to  100  c.cm.  beneath  the  skin,  the  symptoms  disappeared  within 
twenty-four  hours.  This  method  may  be  employed  even  u 
wandering  erysipelas.  Ii  is  then  accessary  to  inject  the  fluid  into 
a  part  of  the  organism  far  from  the  diseased  spot. 

To  sum  up,  barring  a  few  particular  cases,  which  we  have  indicated 
above,  saline  injections  represent  one  of  the  best  methods  of  treat- 
ment of  infectious  diseases.  They  succeed  far  better  in  man  than 
in  animals,  probably  for  the  reason  that  the  nervous  system  in  man 
is  far  more  profoundly  affected.  By  stimulating  its  activity,  the 
injection  favors  general  nutrition  and  the  functions  of  the  principal 
organs.  Moreover,  it  perhaps  acts  also  by  furnishing  water  to  the 
organism.  We  have  several  times  referred  to  the  importance  of  water 
for  the  activity  of  the  cells,  and  if  it  is  true  that  in  the  fight  against 
infections,  the  organism  tends  to  return  to  a  functional  state  char- 
acteristic of  a  younger  age,  the  chemical  formula  of  this  tendency  is 
an  increased  amount  of  water.  This  is  a  new  reason,  based  upon 
numerous  analyses,  for  having  recourse  to  injections  of  salt-water. 

Symptomatic  Medication. 

In  a  great  number  of  cases  the  physician  must  combat  certain 
symptoms  or  complications  regardless  of  the  mechanism  governing 
their  development.  It  is  then  a  question  of  dangerous  or  painful 
disorders,  which  are  about  the  same  in  all  infections,  and  require  a 
common  therapeutics.  Among  these  disorders  several  have  already 
been  studied,  and  we  shall  only  briefly  recall  their  indication.  Of 
others  we  shall  speak  at  some  length. 

Treatment  of  Febrile  Manifestations.  "We  have  sufficiently  indi- 
cated the  rules  that  must  guide  us  in  the  treatment  of  fever  and  have 
shown  that  the  only  rational  medication  is  represented  by  cold  or 
lukewarm  baths.     In  cases  in  which  fever  starts  with  chills  and  in 


820  INFECTIO  US  DISEASES. 

those  iii  whom  chills  occur  in  the  course  of  a  pyretic  infection,  the 
patient  must  be  mechanically  heated.  As  has  already  been  stated, 
chills  represent  a  reaction  of  the  organism  calculated  to  raise  the 
temperature  in  order  to  combat  the  hypothermizing  action  of  toxins. 
At  this,  moment  the  skin  is  cold  and  pale,  owing  to  contraction  of 
the  small  peripheral  arteries.  Since  the  investigations  of  Marey  it 
is  known  that  when  the  skin  is  cold  it  means  that  the  individual 
tends  to  become  heated,  and  that  when  the  skin  is  warm  he  tends 
to  become  cold.  This  formula,  paradoxical  in  appearance,  is,  never- 
theless, very  simple.  When  the  skin  is  cold,  dissipation  of  heat  is 
reduced  as  much  as  possible;  this  dissipation  increases  as  the  cuta- 
neous temperature  rises.  When,  therefore,  the  skin  of  an  individual 
is  cold,  heat  must  be  furnished,  and  when  the  skin  is  warm  heat  must 
be  abstracted.  In  both  instances  naturalistic  medication  is  prac- 
tised. Consequently,  during  chills  the  patient  must  be  well  covered, 
and  hot  water  bottles  should  be  placed  in  his  bed.  Moreover,  to  the 
same  end,  hot  beverages  must  be  given.  This  medication  is  a  popular 
one.  Mistaking  the  effect  for  the  cause,  many  persons  think  that 
the  initial  chills,  notably  in  influenza,  represent  a  cold  which  causes 
the  disease,  and  flatter  themselves  as  to  their  ability  to  arrest  the 
evolution  by  means  of  hot  applications  and  beverages.  The  effect 
is  real,  but  the  interpretation  is  erroneous.  The  truth  is  that  it  is 
not  the  chill  that  is  combated,  but  the  organism  is  assisted  in  warm- 
ing itself. 

At  the  end  and  at  times  during  the  course  of  fevers,  sweating  is 
not  rare.  It  commonly  appears  at  the  end  of  a  paroxysm  after  the 
period  of  heat.  Sweating  requires  some  hygienic  precautions.  The 
perspiration  should  not  be  allowed  to  grow  cold  upon  the  skin.  The 
becl-clothes  should,  therefore,  be  changed,  dry  friction  practised,  and 
the  patient  covered  with  blankets.  Finally,  as  sweating  gives  rise 
to  thirst,  the  patient  must  be  given  drink;  hot  beverages  and  infu- 
sions should  be  administered.  The  sweating  of  cachectic  and  tuber- 
cular patients  requires  special  treatment.  Five  milligrams  of  agaricin 
and  two  to  five  grams  of  camphoric  acid  may  be  prescribed.  The 
best  medicine,  however,  is,  without  doubt,  the  neutral  sulphate  of 
atropin.  One-half  milligram  granules  are  first  given,  and  if  this  dose 
proves  to  be  insufficient,  two,  three,  and  even  four  of  them  may  be 
administered  in  a  day.  Sweating  must  be  combated,  particularly 
during  the  night,  as,  by  its  abundance,  it  disturbs  the  sleep  of  the 
patients.    The  author  has  sometimes  observed  night-sweats  during 


TSEBAPEUTIOS  OF  INFECTIOUS  DI8EA8E8.  821 

convalescence  from  acute  infection  ,  A  granule  of  atropin  given 
three  or  four  evenings  in  succession  suffice*  to  make  them  disappear. 

In  infections  which  terminate  by  cri  i  .  notably  in  pneumonia,  the 
temperature  may  suddenly  fall  below  the  normal.  This  disturbance 
is  transitory  in  adults,  bu1  in  children,  and  <■  pecially  in  the  aged, 
hypothermia  may  be  excessive  and  at  tended  by  alarming  phenomena 
of  collapse.  Hot  baths,  hot  water  bottles,  cutaneom  friction,  and 
stimulating  medicines  musl  then  be  prescribed. 

Treatment  of  Nervous  Manifestations.  The  general  treatment  of 
nervous  disturbances,  whether  the  case  i  one  of  excessive  excitation 
or  depression,  consists  in  lukewarm  or  cold  baths.  'Hi-  if  the  best 
procedure  for  regulating  the  nervous  functions,  remedying  delirium, 
and  inducing  sleep.  It  is  likewise  the  treatment  for  thai  frequent 
and  alarming  symptom  observed  in  children — i.  e.,  convulsions. 
These  are  not  rare  at  the  beginning  of  infections.  ConvulsioM  are 
the  equivalent  of  chills  in  adults.  Commonly  transitory,  they  require 
no  special  treatment.  A  few  hygienic  rules  suffice.  Mosl  parents, 
frightened  at  seeing  their  children  suffering  from  convulsions,  have 
the  deplorable  habit  of  taking  them  in  their  arms,  slapping  them 
on  the  back,  and  walking  the  floor  with  them.  On  the  contrary,  they 
should  be  kept  at  rest.  The  child  should  be  placed  in  a  large  bed 
so  as  to  avoid  the  danger  of  falling  out  when  agitated.  The  room 
should  be  kept  in  semidarkness  and  free  from  noise.  When  convul- 
sions are  repeated  the}'  indicate  a  lesion  in  the  nervous  centres  or  a 
too  great  excitability  of  the  child.  In  the  latter  case  they  are  the 
equivalent  of  delirium.  It  is  then  necessary  to  resort  to  lukewarm 
baths  at  100.5°  F.  (38°  C.)  during  the  intervals  of  convulsion,  or,  if 
fever  is  intense,  to  baths  gradually  rendered  cold  so  as  to  reach 
a  temperature  of  S9.5°  or  even  86°  F.  (32°  or  30°  C).  For  the 
same  purpose  antispasmodic  preparations  may  be  employed,  among 
which  the  most  usual  are  the  tinctures  of  musk,  asafetida,  and  vale- 
rian, which  are  prescribed  in  doses  of  ten  to  thirty  drops,  according 
to  the  age  of  the  children.  In  the  case  of  gastric  intolerance,  a  musk 
enema  is  generally  given. 

The  treatment  of  delirium  requires  special  consideration.  Balneo- 
therapy takes  the  first  rank.  In  young  and  robust  adults  cold  baths 
are  given.  In  children  and  persons  above  forty  years  of  age.  luke- 
warm baths  are  administered.  It  is  well  to  note,  however,  that  in 
these  cases  cold  effusions  should  be  practised  upon  the  head  during 
the  bathing.    If  the  patient  is  much  agitated,  for  instance,  in  the 


822  INFECTIOUS  DISEASES. 

case  of  alcoholic  delirium,  an  additional  difficulty  faces  us.  After 
having  been  brought  back  to  his  bed,  the  patient  may  attempt  to 
get  out  and,  even  when  constantly  watched,  he  may  at  times  succeed 
in  rising.  It  is  then  necessary  to  force  him  to  lie  down  again.  In 
hospitals  the  difficulties  are  still  greater,  and  physicians  are  some- 
times compelled  to  resort  to  coercive  measures.  One  of  the  best 
methods,  which,  however,  is  applicable  only  to  mild  cases,  consists 
in  placing  on  each  side  of  the  bed  a  plank  so  as  to  prevent  an  easy 
escape.  When  delirium  is  more  intense  it  is  necessary  to  bind  the 
patient,  but  in  such  a  maimer  as  to  allow  him  to  move  easily  in  the 
bed. 

The  therapeutic  indications  vary  according  to  the  cases  under 
treatment.  There  is  a  neuropathic  delirium  related  to  a  previous  state 
of  the  individual,  and  there  is  a  delirium  dependent  upon  chronic 
intoxications,  notably  alcoholism.  Neuropathic  delirium,  when  not 
very  intense,  requires  no  special  therapeutics.  Balneotherapy  is 
sufficient.  When  intense,  delirium  must  be  treated  by  means  of  anti- 
spasmodics. Bromides  may  render  service.  In  infectious  diseases, 
which  are  so  often  attended  by  cardiac  or  renal  disturbances,  it  is 
well,  in  general,  to  avoid  potassium  salts.  Bromide  of  sodium  should 
be  given  in  doses  of  from  two  to  four  grams  a  day.  Musk  is  also 
available,  but  the  medicine  to  which  the  author  resorts  most  fre- 
quently is  valerian.  The  best  preparation  is  the  extract,  of  which 
4  to  6  grams  are  given  a  day.  An  infusion  of  the  root  is  also  useful, 
15  to  30  grams  of  which  may  be  given  as  an  enema,  or  a  10: 1000 
infusion  of  half  an  hour.  Valerian  acts  mostly  by  the  isomeric  carbo- 
hydrate of  turpentine  oil,  which  it  contains,  and  not  by  valerianic 
acid.  The  author,  therefore,  avoids  the  use  of  valerianate  of  am- 
monia. 

In  alcoholic  delirium  occurring  in  the  course  of  an  infectious  dis- 
ease, the  extract  of  valerian  may  be  employed.  The  true  medication, 
however,  is  alcohol  associated  or  not  with  opium.  In  our  hospitals 
Todd's  potion  is  usually  prescribed.  The  French  Codex  formulates 
it  in  the  following  manner:  old  brandy  or  rum,  40  grams;  simple 
syrup,  30  grams;  tincture  of  cinnamon,  5  grams;  distilled  water, 
75  grams. 

As  brandv  and  rum  contain  45  to  60  per  cent,  of  alcohol,  the 
amount  given  above  is  too  small.  In  fact,  Todd  prescribed  from 
100  grams  to  150  grams  of  brandy  in  twenty-four  hours  for  cases  of 
medium  severity,  and  from  300  to  500  grams  in  grave  cases.    The 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  W, 

second  Indication,  however,  formulated  by  Todd,  and  which  u  per 
haps  the  most  important  but  is  often  overlooked,  i   thai  the  alcoholic 
potion  is  not  to  be  given  in  very  large  do  e  .     According  to  'In- 
famous clinician,  II  grams  of  brandy  should  be  given  ev< 
hours.    If  this  precept  is  no!  followed,  grave  accidents  may  I"-  pro 
duced  by  the  use  of  this  alcoholic  beverage.    A  very  simple  procedure 
consists  in  giving  a  dessertspoonful  of  rum  with  two  or  three  timet 
its  volume  of  sweetened  water  every  two  hours.    If  the  agitation  i- 
extremely  violent,  alcohol  may  be  associated  with  opium.   This  ■ 
ciation  is  frequently  in< lic-i I «•< I  in  pneumonia,  erysipelas,  and  variola. 
From  5  eg.  to  10  eg.  of  extracl  of  opium  or  from  20  to  1()  drops  of 
Sydenham's  laudanum  is  given   in   twenty-four  hours.     The  opium 
preparations  are  likewise  to  be  given  in  fractional  doses.     The  desired 
quantity  may  be  given  in    Todd's  potion  or  with  wine.     Wine  to 
which  the  daily  dose  of  laudanum  is  added  has  s  very  remarkable 
action;  one  litre  of  such  wine  may  be  given  in  twenty-four  hours. 
If  there  is  tendency  toward  adynamia,  champagne  is  to  he  preferred. 
The  treatment  must  be  completed  by  certain  medicines  calculated 
to  combat  cardiac  disorders  which  are  so  frequent  in  such  a 
Spartein  and  strychnine  may  be  administered  subcutaneously.    One 
cubic  centimetre  of  a  solution  containing  5  eg.  of  sulphate  of  spartein 
and  1  mg.  of  sulphate  of  strychnine  may  be  injected  morning  and 
evening. 

This  treatment  would  be  perfect  if  the  cerebral  disorders  of  alco- 
holic patients  did  not  frequently  coexist  with  renal  lesions.  Albu- 
minuria absolutely  contraindicates  the  employment  of  alcohol  and 
of  opium,  which  then  produce  extremely  grave  phenomena  of 
depression.  Baths,  bromides,  and  valerian  will  suffice  in  such  a  -  - 
Moreover,  let  us  recall  that,  in  certain  cases,  delirium  may  be  cured 
by  specific  medication.  Quinine  should  be  given  in  the  case  of 
malarial  delirium  and  mercury  and  iodides  to  syphilitica. 

When  the  nervous  system  is  much  excited  insomnia  is  frequent. 
This  disturbance  is  combated  by  the  medications  directed  against 
delirium  and  by  the  general  therapeutics  of  infection.  If.  notwith- 
standing the  baths,  insomnia  should  persist,  hypnotics  must  be 
employed.  As  the  patients  soon  become  accustomed  to  their  action, 
it  is  well  to  change  the  medicine  as  soon  as  its  effect  is  exhausted. 
One  gram  of  sulphonal,  of  trional,  or  of  hypnal,  2  grams  of  chloral 
hydrate,  or  a  mixture  of  chloral  and  bromide  of  sodium,  in  the  dose 
of  1  gram  of  each,  may  be  administered.     Opium  should  be  mis- 


8  2  4  IXFECTIO  US  DJSEA  SES. 

trusted.  It  is  indicated  only  in  alcoholic  patients  and  in  the  course 
of  variola.  Even  in  these  cases,  however,  it  is  to  be  avoided  if  there 
is  albumin  in  the  urine  or  the  secretion  is  too  scanty.  In  children 
lukewarm  baths  almost  always  suffice.  In  case  of  need  a  little 
bromide  of  sodium  or  calcium  may  also  be  prescribed;  20  eg.  or 
25  eg.  for  each  year  of  the  age  may  be  administered. 

^'hen  the  nervous  system  seems  to  be  exhausted,  diffusible  stimu- 
lants are  to  be  resorted  to.  Potions  containing  rum  or  brandy,  cham- 
pagne, and  vinous  beverages  may  be  prescribed.  Wine  may  be  given 
to  children;  30  to  60  grams  of  Malaga  would  be  an  excellent  dose. 
The  wine  of  Bagnols  is  used  in  the  cordial  potion  of  the  French 
Codex:  110  grams  of  Bagnols,  40  grams  of  syrup  of  bitter  orange- 
peel,  10  grams  of  tincture  of  cinnamon.  Coffee  and  preparations  of 
caff  em  may  likewise  be  employed. 

Among  stimulants,  ether  may  be  utilized.  Thirty  grams  of  syrup 
of  ether  is  given  in  a  julep  to  which  four  grams  of  acetate  of  ammonia 
are  added.  Ether  may  likewise  be  administered  subcutaneously.  The 
injections  must  be  made  quite  deep  into  the  tissues;  otherwise  they 
are  very  painful,  and,  what  is  graver,  at  times  give  rise  to  small 
eschars.  One  or  two  cubic  centimetres  of  pure  ether  is  generally 
injected,  and  may  be  repeated  every  hour.  Du  Castel  has  emphasized 
the  satisfactory  effects  obtained  in  variola  by  the  combined  treat- 
ment of  ether  and  opium.  One  cubic  centimetre  of  ether  is  injected 
morning  and  evening,  and  from  6  eg.  to  10  eg.  of  extract  of  opium 
are  at  the  same  time  prescribed,  according  to  the  severity  of  the 
delirium. 

The  injections  of  ether  may  with  advantage  be  replaced  by  those 
of  camphorated  oil.  A  1: 3  solution  is  employed;  in  some  cases  one- 
tenth  of  ether  is  added  to  it.  Camphor  exercises  a  powerful  dyna- 
mogenic  action  upon  the  nervous  system.  It  may  be  administered 
in  the  form  of  enema ;  in  this  case  it  is  suspended  in  a  gum  arabic 
emulsion  containing  in  250  grams  of  the  fluid,  1  gram  of  camphor, 

2  grams  of  gum  arabic,  and  the  yolk  of  one  egg. 

Among  the  nervous  disturbances  of  convalescents  we  may  cite 
various  paralyses  which  may  be  treated  by  two  procedures :  an  inter- 
nal treatment  represented  by  strychnine,  given  in  doses  of  2  mg.  or 

3  mg.  of  the  sulphate  or  the  arsenate;  an  external  treatment  repre- 
sented by  electric  currents.  If  there  is  albuminuria  at  the  same 
time,  electricity  alone  is  to  be  employed.  Faradic  currents  are 
generally  used. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

Treatment  of  Cardiovascular  Manifestations.    I  [carl  disturbance* 
are  so  frequent  and  importanl  in  various  infection   thai  the: 
particular  attention  and  often  require  special  treatment. 

The  physician  has  seldom  to  combal  erethism.  [1  ometimes 
()(.(.,ii-s  in  the  beginning  of  pericarditis.  The  therapeutic  indications 
consist  mainly  in  revulsive  measures:  dry  or  we\  cupping  over  the 
precordial  region  and  thermocauterization  may  daily  be  applied. 
Coincidently,  bromide  of  sodium  or,  whal  seen,,  to  be  preferable,  a 
mixture  of  2  grams  of  the  bromide  and  I  gram  of  iodide  of  sodium 
may  be  prescribed.  The  vasodilatation  produced  by  the  latter  medi- 
cine diminishes  cardiac  erethism  and  the  painful  phenomena  accom- 
panying it.  II'  Hie  latter  arc  very  marked,  opium  preparations,  auch 
as  Dover's  powder  or  injections  of  morphine,  may  al  the  same  time 
be  prescribed.  In  most  cases  the  period  of  excitation  is  transitory 
and  too  often  yields  to  a  state  of  depression  depended  upon  myo- 
carditis. 

Whatever  may  be  its  cause,  myocarditis  has  importanl  therapeu- 
tic indications.    The  first  question  arising  is:   Should  the  cold  baths 
be  continued?    It  is  true  that  patients  who  receive  baths  are  less 
frequently  liable  to  develop  myocarditis.    When,  however,  it  is  devel- 
oped the  baths  should  be  suspended.    In  fact,  the  first  indication  con- 
sists in  the  avoidance  of  all  movement  and  all  displacement  of  the 
patient.    Coincidently,  alcohol  or  coffee  are  to  be  prescribed;  injec- 
tions of  ether,  of  camphorated  oil,  and,  above  all.  subcutaneous 
injections  of  artificial  serum,  must  be  practised,  the  latter,  however, 
in'  small  amounts  often  repeated.     Among  cardiac  medicines,  digi- 
talis is,  in  this  connection,  the  least  effectual;  5  eg.  of  sulphate  of 
spartein,  tincture  of  strophantus,  or  strophanthin,  and  especially 
caffein,  are  to  be  employed.    If  the  symptoms  are  not  too  serious, 
caffein,  given  in  a  potion,  will  suffice.    It  is  dissolved   by  benzoate 
of  soda,  the  influence  of  which  upon  oxidations  is  appreciable.    In 
this  case  the  author  prescribes  a  stimulating  potion  formulated  as 
follows:  rum,  30  grams:  syrup  of  bitter  orange-peel,  30  grams:  Hoff- 
man's anodyne,1  4  grams:  tincture  of  cinnamon,  2  grams:  benzoate 
of  soda,  4  grams:   caffein,  1  gram:   linden  flower  water,  60  grams. 
One  tablespoonful  every  half  hour  is  taken. 

In  case  of  urgency,  subcutaneous  injections   must  be  practised. 
The  classical  solution  is  then  employed:  benzoate  of  soda.  3  grams: 

»  The  French  preparation  of  Hoffman's  anodyne  consists  of  equal  parts  of  ether  and 

alcohol.  90°.— Translator. 


826  INFECTIOUS  DISEASES. 

caffein,  2.5  grams;  distilled  water,  sufficient  quantity  to  make 
10  com.  Each  Pravaz  syringeful  contains  25  centigrams  of  caffein; 
three  or  four  injections  may  be  given  in  twenty-four  hours.  When 
the  phenomena  of  collapse  appear,  injections  of  caffein  are  to  be 
alternated  with  those  of  ether,  or  camphorated  oil,  or  sulphate  of 
strj^chnine,  of  which  1  milligram  is  injected  twice  a  day.  Lastly, 
when  arterial  pressure  is  very  low — Potain  has  seen  it  fall  to  13  or 
even  6  cm. — a  little  ergotin  ma)*-  be  given.  In  case  of  fainting,  the 
habitual  means  are  employed:  horizontal  decubitus,  the  head  a 
little  low,  flagellation,  artificial  respiration,  and  rhythmic  traction 
of  the  tongue. 

If  the  patient  recovers,  he  is  to  be  kept  on  milk  diet  for  a  long 
time,  and  the  avoidance  of  movements  and  displacements  must 
be  emphasized.  Finally,  some  cardiac  medicine  must  be  prescribed, 
among  which  I  prefer  strophanthus  (1  to  2  milligrams  of  the  extract 
or  ten  to  fifteen  drops  of  the  tincture) .  The  hypertrophy  consecutive 
to  infections  requires  no  special  treatment.  The  treatment  of 
chronic  cardiopathies  is  to  be  applied — i.  e.,  hygienic  precautions 
and  avoidance  of  fatigue.  As  to  pharmaceutical  measures,  long- 
continued  medication  with  iodide  and  bromide  yields  the  most 
satisfactory  results. 

For  twenty  days  each  month  a  daily  dose  of  1  gram  of  bromide 
of  sodium  and  80  eg.  of  iodide  of  sodium,  with  20  eg.  of  iodide  of 
potassium,  should  be  given. 

Endocarditis  is  less  frequent  and  requires  no  special  therapeutics. 
At  the  beginning,  treatment  is  the  same  as  in  pericarditis.  In  case 
of  need,  cardiac  erethism  must  be  quieted  by  means  of  revulsives. 
If  the  heart  muscle  shows  signs  of  failure,  the  same  treatment  as 
for  myocarditis  may  then  be  prescribed. 

Vascular  and  notably  arterial  complications  are  very  rare.  Should 
the  aorta  be  affected,  the  treatment  must  consist  in  revulsive 
measures.  In  the  case  of  peripheral  arteritis,  the  first  indication  is 
to  place  the  affected  limb  in  a  good  position  and  surround  it  with 
hot  compresses.  When  ischemia  terminates  in  sphacelation,  sub- 
cutaneous injections  of  antiseptic  substances  must  be  resorted  to. 
The  author  employs  neutralized  peroxide  of  hydrogen.  Bouchard 
obtained  success  by  interstitial  injections  of  creosote.  Formol  and 
camphorated  salol  have  likewise  been  employed  for  the  same  pur- 
pose. If  the  gangrene  extends  or  the  general  state  is  aggravated, 
amputation  must  be  practised. 


THERAPEUTICS  OF  INFECTIOUS  DISEASES.  827 

Treatment  of  Respiratory  Manifestations.    Respirator)  di  01 
require  very  active  therapeutics,    [n  the  firsl  place  the  nasal  foci 
may  ho  the  seat  of  a  serous,  mucous,  or  purulenl  catarrh. 

Iii  some  cases  the  inflammation  extends  to  the  inn  e  of  the  face. 
In  tho  caso  of  a  simple  serous  catarrh,  a  slightly  antiseptic  powder 
is  snuffed  or  a  little  menthol  is  inhaled.  In  the  case  of  purulent 
coryza  1-1 10  host  treatment  consists  in  menthol  inhalations.  The 
vapor  penetrates  into  the  interiorof  the  nose  and  even  the  -n 
and  realizes  a  certain  degree  of  antisepsis.  A  tablespoonful  of  a 
3  per  cent,  alcoholic  solution  of  menthol  is  pul  in  a  howl  of  hot  water* 
which  is  then  covered  with  a  funnel  turned  down,  and  the  patienl 
is  instructed  to  breathe  the  vapors  rising  through  the  tube  of  the 
funnel.  In  more  serious  cases,  lavage  must  be  resorted  to  accord- 
ing to  the  procedures  which  wo  have  already  indicated.  Then  a 
salve  with  resorcin  and  menthol  must  be  introduced.  The  em- 
ployment, of  menthol  in  the  form  of  inhalations  and  of  salves  is 
the  best  treatment  to  oppose  the  development  of  sinusites.  Lastly, 
it  is  well  to  remember  that  the  discharges  from  the  nose  often 
irritate  the  upper  lip;  hence  the  epidermis  must  be  protected  by 
means  of  a  salve,  such  as  vaselin  containing  boric  acid  or  bismuth. 
When  lesions  involve  the  larynx,  menthol  inhalations  may  likewise 
be  employed.  The  medicinal  vapor  thus  reaches  the  entire  upper 
part  of  the  respiratory  tract.  It  is  advisable,  at  the  same  time,  to 
keep  the  patient  in  a  rather  humid  atmosphere.  For  this  purpose 
slightly  antiseptic  fluids,  such  as  earbolized-water  or  benzoin-water, 
may  be  sprayed  about  the  patient.  If  the  lesions  are  more  profound . 
notably,  if  they  terminate  in  the  production  of  ulcerations,  stronger 
medication  is  necessary.  Spraying  should  be  done  with  Van  Swieten's 
solution,or  with  naphtholated  water.  The  latter  medicine  is  em]  »1<  ryo  1 
as  follows:  25  eg.  of  naphthol  in  25  c.cm.  of  alcohol  and  75  c.cm.  of 
water.  In  rare  cases  it  may  be  necessary  to  touch  the  larynx  directly 
by  certain  local  medicines.  Some  medicines  administered  by  the 
mouth  may  exercise  a  favorable  action  upon  the  larynx:  some  of 
them  stimulate  the  secretions,  others  dimmish  the  spasmodic 
element  which  is  superadded  to  the  inflammatory  process.  Nitrate 
of  pilocarpin  is  very  serviceable  in  the  former  case.  I  inject  sub- 
cutaneously,  at  two  different  times,  \  c.cm.  of  a  1  per  cent,  solution. 
The  spasmodic  element  must  be  combated  by  belladonna  frequently 
associated  with  aconite.  A  mixture  of  equal  parts  of  tincture  of 
belladonna  and  aconite  root  is  used,  thirty  drops  a  day  in  three 


828  INFECTIO  US  DISEASES. 

doses.  Bromides,  bromoform,  and  codein  may  also  be  used  for  the 
same  purpose. 

We  should  like  to  call  special  attention  to  the  frequency  of  ex- 
tremely troublesome  night  coughing  in  certain  infections  and  par- 
ticularly certain  epidemics  of  influenza.  These  coughing  spells 
sometimes  last  an  hour  or  more  and  give  rise  to  great  fatigue.  The 
true  treatment  consists  in  giving,  at  the  moment  of  the  spell,  one  or 
two  tablespoonfuls  of  the  following  potion  in  a  little  water:  bromo- 
form, 1  gram ;  syrup  of  codein,  40  grams ;  cherry-laurel  water,  5  grams ; 
white  looch,  80  grams. 

Applications  upon  the  cervical  region  are  quite  frequently  prac- 
tised. They  may  be  employed  cold  or  hot.  In  the  former  case 
the  intention  is  to  exercise  an  antiphlogistic  action.  Hot  applications, 
however,  are  being  more  and  more  resorted  to,  as  they  are  anti- 
spasmodic, and  at  the  same  time  stimulate  reactions.  Laryngeal 
spasm,  notably  in  young  children,  may  very  rapidly  be  soothed  by 
means  of  hot  applications  upon  the  neck,  and  at  the  same  time  by 
inhalation  of  steam.  When,  in  spite  of  all  these  medications,  the 
disturbances  persist,  when  the  spasm  becomes  too  intense  or  lasts 
too  long,  or  when  an  obstacle  to  the  entrance  of  air  results  from  deep 
lesions,  pseudomembranes,  edema,  or  ulcerations,  the  passage  of  air 
should  be  re-established  by  tracheotomy. 

As  is  known,  bronchitis  is  extremely  frequent  in  the  course  of  the 
most  varied  infections.  When  slight,  it  needs  no  particular  treat- 
ment. When  intense,  bronchitis  does  not  contraindicate  balneo- 
therapy. On  the  contrary,  the  baths  should  be  continued,  even 
cold  baths;  under  their  influence  vascular  constriction  is  produced, 
which  reduces  the  congestive  phenomena.  If  the  individual  is  too 
nervous,  or  if  too  violent  excitation  is  feared  for  some  reason  or 
other,  warm  baths  at  96.8°  or  even  100.4°  F.  (36°  or  38°  C.)  may  be 
given  every  three  hours.  This  treatment  is  also  indicated  when  the 
inflammation  extends  to  the  small  bronchi  and  terminates  in  broncho- 
pneumonia. At  the  same  time  applications  to  the  chest  may  be 
employed.  They  are  useful  in  all  complications  of  the  respiratory 
apparatus.  The  heating  compress  gives  excellent  results.  A  piece 
of  muslin  is  folded  eight  or  ten  times  and  immersed  in  water  at 
59°  or  even  50°  F.  (15°  or  10°  C).  It  is  then  wrung  out  and  applied 
upon  the  chest  of  the  patient  and  covered  with  oiled  silk.  At  the 
end  of  two  or  three  hours  the  compress  is  removed.  The  chest  is 
then  found  very  hot  and  the  skin  red  and  congested,  as  if  a  sinapism 


THERAPEUTICS  OF  INFECTIOUS  DISEASES. 

had  been  applied.  The  treatment  acts  by  the  revulsion  and  the 
aervous  excitation  which  H  induces,  which  resull  in  deeper  respira- 
tion and  at  times  in  :i  spell  of  coughing  which  expel    muco  itii 

Cutaneous  revulsion  may  also  be  practiced  by  meant  of 
poultices  sprinkled  with  mustard  Hour,  and  dry  and  wel  cupping, 
[f  the  lesions  are  circumscribed,  tincture  of  iodin  may  be  used  to 
which  a  little  guaiacol  is  added  in  the  proportion  of  2:  LO  or  5:  I". 
or  a  salve  with  guaiacol  in  the  proportion  of  I  \  ;  10  or  1 :  10.  It  i- 
better  (,<>  abstain  from  vesica  tones  which,  in  an  organism  already 
infected,  may  aggravate  the  urinary  disturbances  and  even  cause 
cutaneous  lesions,  and  thus  open  a  route  for  secondary  infection. 
Finally,  in  children,  a  more  extensive  revulsive  action  may  be 
exercised  by  prescribing  lukewarm  mustard  baths:  150  or  200  grama 
of  mustard  (lour  is  put  in  a  linen  bag,  which  is  first  plunged  into  cold 
water,  then  into  the  water  of  the  bath.  In  very  young  children 
revulsion  is  obtained  by  means  of  hot  friction.  Camphorated 
chamomile  oil  is  put  in  a  cup  and  heated  over  the  flame  of  a  candle, 
and  then  hot  friction  is  practised  with  the  hand  upon  the  abdomen 
and  lower  extremities,  which  are  then  covered  with  a  thick  layer 
of  cotton.  As  to  the  degree  of  temperature  at  which  the  oil  is  to 
be  used,  it  is  not  necessary  to  determine  it  accurately.  The  parents 
should  be  instructed  to  employ  it  as  hot  as  the  hand  can  bear. 

These  various  procedures  are  designed  to  produce  revulsion. 
They  sometimes  succeed  in  palliating  certain  disorders.  There  is 
one  disturbance,  however,  which  gives  much  trouble  to  patients 
and  against  which  some  remedy  is  always  asked:  We  refer  to  cough- 
ing. Let  us  remark  immediately  that  coughing,  although  very 
troublesome,  is  nevertheless  useful  at  least  in  certain  instances.  We 
must  distinguish  two  kinds  of  cough:  one  is  dry  and  spasmodic,  the 
other  favors  expectoration.  The  former  may  be  combated,  the 
latter  must  be  respected,  for  it  is  intended  to  eliminate  bronchial 
secretions  or  exudates  of  the  bronchi  and  lungs.  Various  soothing 
medicines  may  be  prescribed  against  dry  cough:  antispasmodics 
especially  opium  preparations  are  useful.  Nearly  all  cough  syrups 
contain  opium.  The  following  are  very  often  prescribed:  Di:. 
syrup,  which  contains  1  eg.  of  extract  of  opium  to  20  grams  of  syrup; 
syrup  of  morphine,  containing  1  eg.  of  this  alkaloid  to  20  grams  of 
syrup:  syrup  of  codein,  20  grams  of  which  represent  4  eg.  oi  codein; 
the  opiated  syrup  of  lactucarium  of  the  French  Coder,  which  contains 
5  mg.  of  extract  of  opium  and  1  eg.  of  extract  of  lactucarium  in 


830  INFECTIOUS  DISEASES. 

20  grams  of  syrup.  These  various  syrups  are  often  mixed  with 
syrup  of  belladonna  and  cherry-laurel  water. 

Even  when  coughing  serves  expectoration,  it  may  be  combated 
by  the  various  therapeutic  procedures  above  indicated.  For, 
although  it  is  useful,  it  sometimes  is  so  troublesome  as  to  disturb 
the  rest  of  the  patient  and,  therefore,  must  be  moderated.  In  this 
case,  however,  it  is  advisable  to  abstain  from  opium  preparations 
and  resort  to  expectorants.  Emetics  are  at  times  prescribed  for 
this  purpose.  This  medication,  which  renders  appreciable  service, 
is  generally  well  borne  by  children.  The  child  being  incapable  of 
expectorating,  the  spasmodic  shaking  of  the  cough  exercises  a  sort 
of  massage  of  the  lung,  and  thus  serves  for  expectoration  of  the 
exudates  encumbering  the  respiratory  passages.  Ipecac,  however, 
which  is  the  only  emetic  available,  should  not  be  administered  except 
when  infection  is  of  moderate  severity  and  the  child  vigorous; 
otherwise  it  may  cause  depression  and  collapse.  On  the  other  hand, 
an  emetic  is  seldom  indicated  in  adults,  and  should  never  be  pre- 
scribed for  those  above  forty  years  of  age.  If  bronchial  secretions 
are  profuse  or  the  congestive  phenomena  intense,  ipecac  is  employed 
in  fractional  closes.  For  this  purpose  Dover's  powder  may  also  be 
employed.  The  preparations  of  antimony  are  likewise  regarded  as 
expectorants.  Ammonium  salts  are  also  useful  in  this  connection. 
The  Germans  frequently  prescribe  hydrochlorate  of  ammonia.  In 
France  the  acetate  of  ammonia  is  mostly  used  in  doses  of  from 
2  to  4  grams  daily.  It  is  usually  associated  with  20  or  30  grams 
of  syrup  of  ether.  In  cases  in  which  the  urine  is  very  albuminous, 
we  prefer  benzoate  of  soda  in  daily  doses  of  from  2  to  6  grams.  If 
after  the  fall  of  fever  the  thoracic  manifestations  persist,  balsamic 
preparations  may  be  resorted  to  and,  if  the  process  passes  to  a 
chronic  state,  sulphurous  medicines  may  be  employed.  Among 
balsamics  the  balsams  of  Tolu  and  terpin  are  most  frequently 
employed. 

These  general  rules  must  be  supplemented  by  a  few  special  indi- 
cations. When  there  is  tendency  toward  passive  congestion  the 
patient  must  be  instructed  to  lie  down  in  a  certain  manner.  If 
possible,  he  should  sit  in  an  arm  chair  or  in  his  bed.  He  must  at 
least  avoid  keeping  the  same  position.  He  should  lie  down  on  one 
side,  sometimes  on  the  left,  sometimes  on  the  right.  The  blood 
circulation  is  to  be  modified  by  means  of  revulsives  and  repeated 
cupping.     Certain  medicines  may  likewise  serve  to  regulate  the 


THERAPEUTICS  OF  INFECTIOUS  diseases.  .-.;\ 

circulation.  Some  of  them  acl  directly  upon  the  pulmonary  blood- 
vessels, others  exerl  an  indirect  action  through  the  heart.  Among 
the  former,  ergotin  may  especially  be  mentioned;  among  the  latter 
digitalis,  cafTein,  and  strophanthus.  Moreover,  if  a  phyxia  oc< 
inhalation  of  oxygen  Is  useful,  and  in  ca  e  of  need,  scarified  cupping 
or  a  genera]  blood-letting  may  be  pracl  ised  if  the  patienl 
subject. 

When  putrid  fermentations  are  produced  in  the  bronchial  exudi 
recourse  is  to  he  had  to  substances  which,  being  eliminated  by  the 
respiratory  passages,  may  exert  an  antiseptic  action  thereon.  For 
this  purpose  tincture  of  eucalyptus  is  generally  given  in  doa 
2  grams,  and  subcutaneous  injections  of  eucalyptol:  5  to  10  c.cm. 
of  a  solution  in  oil  (in  the  proportion  of  2  or  '■'>  per  cent .)  are  injected. 
Finally,  hyposulphite  of  soda  also  exercises  an  appreciable  action 
upon  the  bronchial  secretions:  from  4  to  6  grams  of  it  are  given 
daily.  All  these  medications  produce  no  well-marked  effect  upon 
the  putrefactions  of  the  respiratory  apparatus.  They  seem,  however. 
to  act  more  effectually  than  inhalations  of  medicinal  substances, 
such  as  turpentine  and  eucalyptus.  When  a  well-localized  focus  is 
found  in  the  lung,  one  is  always  irresistibly  tempted  to  apply  to  it 
some  local  medicine.  Attempts  have  been  numerous,  but  without 
encouraging  results.  Intrapulmonary  injections  expose  to  consider- 
able dangers;  hence,  they  have  been  almost  entirely  abandoned. 
The  best  intervention  is  evidently  incision  and  drainage  of  the 
morbid  focus,  provided,  of  course,  that  the  lesion  is  circumscribed. 
There  is,  however,  no  chance  of  success  except  in  the  case  of  indi- 
viduals primarily  affected,  viz.,  in  those  who  are  sufficiently  robust. 
Even  then  the  operation  is  always  more  or  less  unsafe,  especially 
in  view  of  the  danger  from  secondary  hemorrhages,  which  are  of 
frequent  occurrence. 

Treatment  of  Disorders  of  the  Digestive  Apparatus.  Digestive 
disturbances  often  hinder  the  therapeutics  of  infectious  disi  -  - 
Vomiting  is  observed  at  the  start  of  a  great  number  of  infections. 
They  seem  to  be  dependent  upon  some  disorder  of  innervation.  In 
the  majority  of  cases  the  manifestation  is  transitory  and  requires 
no  treatment.  Should  vomiting  fatigue  the  patient  too  much  or 
last  too  long,  it  may  be  allayed  by  cold  applications  upon  the 
epigastric  region:  an  ice-bag  is  placed  or  ether  is  sprayed  upon  the 
region.  At  the  same  time  the  patient  may  be  given  cold  and  slightly 
acidulated  beverages  to  drink:  or  a  small  quantity  of  champagne 


832  IXFECTIO  US  DISEASES. 

with  a  little  Seltzer  water  may  be  given.  If  more  active  intervention 
is  necessary,  the  classical  potion  of  Riviere1  is  prescribed.  The 
nature  of  such  vomitings  being  known,  however,  we  prefer  medicines 
which  soothe  the  reflex  sensitiveness  of  the  stomach :  chloroform- 
water  and  belladonna  seem  to  me  indicated.  We  prescribe  a  mixture 
of  100  grams  of  saturated  chloroform-water ;  20  grams  of  syrup  of 
belladonna,  and  5  grams  of  cherry  laurel-water,  1  tablespoonful  to 
be  taken  every  hour  or  half  hour.  During  the  stationary  period 
vomiting  depends  either  upon  defective  secretion  or  a  gastric  local- 
ization, or  else  upon  some  complication. 

"We  often  see  patients  who,  under  normal  conditions,  take  milk 
with  pleasure  and  digest  it  well,  while  in  the  course  of  infections 
they  can  no  longer  bear  it;  they  vomit  it  in  the  form  of  large  curds 
shortly  after  they  have  taken  it.  In  this  case  milk  may  be  mixed 
with  some  alkali,  such  as  Vichy,  Vals  water,  and,  especially  when 
there  is  diarrhea,  lime-water.  Should  this  prove  insufficient,  the 
digestion  must  be  assisted  by  pancreatin.  This  may  be  given  in 
the  form  of  pills  after  each  cup  of  milk,  or  20  to  30  eg.  of  it  may 
be  added  to  the  milk  at  the  time  of  administration.  Another  method 
consists  in  giving  a  small  amount  of  beer  yeast,  which  facilitates 
considerably  the  digestion  of  milk.2 

It  should  not  be  overlooked  that  vomiting  is  often  due  to  medicines 
prescribed.  Hence,  in  many  cases,  discontinuance  of  a  potion  suffices 
to  re-establish  the  digestive  functions.  In  this  regard  alcohol  and 
cinchona,  which  are  so  often  abused,  have  an  unfavorable  influence 
which  should  be  remembered.  When  vomiting  results  from  gastric 
localization,  more  active  therapeutics  must  be  employed.  If  the 
question  is  one  of  simple  catarrh,  lavage  of  the  stomach  will  render 
service.  If  it  is  due  to  ulcer,  for  example,  it  is  expressed  by  vomiting 
of  sanguinolent  matters,  and  the  stomach  must  be  given  absolute 
rest.  No  nourishment  or  beverages  should  be  given  by  the  mouth; 
nutritive  enemas  and  hypodermic  injections  of  salt-water  must  be 
given.  Ice  is  to  be  applied  upon  the  h}^pogastric  region,  and  opium 
given  either  in  the  form  of  pills  of  extract  of  opium,  of  which  1  eg. 
may  be  administered  every  hour,  or  in  the  form  of  subcutaneous 
injections  of  morphine.     The  latter  method  has  the  advantage  of 

1  "Potion  de  Riviere"  has  the  following  composition  :  potassium  bicarbonate,  4  grams; 
simple  syrup,  30  grams;  water,  100  grams. — Translator. 

2  Matzoon  or  zoolak  is  very  often  used  in  America  as  a  substitute  for  milk  when  the 
latter  is  not  well  borne. — Translator. 


THERAPEUTICS  OF  INFECTIOUS  DI8EA8E8. 

acting  more  promptly.  Moreover,  hemorrhage!  ma)  I"  am  ted  by 
making  a  sort  of  gasl  ric  dressing  by  means  of  subnitrate  oi  bismuth; 
u  large  dose  of  the  latter  should  be  prescribed ;  15  and  <■:  en  M I 
would  Dot  be  too  much.  Vomiting  due  to  complications  requires 
no  special  therapeutics.  Ii  is  dependenl  upon  nephritis,  meningiti  . 
perforation  of  the  intestine,  and  sometimes  to  inflammation  of  the 
diaphragmatic  pleura.  If,  however,  it  becomes  alarming,  the  vomit- 
ing may  be  combated  by  the  various  methods  already  referred  to. 
and  which  are  to  be  modified  according  to  circumstance  I 
instance,  opium  may  be  given  in  case  of  peritonitis,  while  this  drug 
is  to  be  avoided  when  there  is  uremia. 

Finally,  at  the  moment  of  convalescence,  persistenl  vomiting 
formerly  observed  when  the  patient  was  firsl  given  nourishment. 
At  present,  however,  the  method  of  absolute  did  having  been 
abandoned,  nothing  of  the  kind  is  any  longer  encountered.  The 
vomiting  of  convalescence  is  due  to  some  complication  or  to  hysteria. 
In  the  latter  instance,  it  rapidly  yields  to  the  usual  procedures. 
Finally,  in  consequence  of  diphtheria,  vomiting  may  depend  upon 
gastric  paralysis.  It  then  occurs  in  the  form  of  regurgitations.  In 
this  case  lavage  may  cause  death.  The  introduction  of  a  considerable 
amount  of  fluid  into  the  stomach  has  at  times  been  followed  by  the 
rejection  of  matters  which  have  passed  into  the  respiratory  truer. 
The  patients  should,  therefore,  be  given  small  quantities  of  food, 
preferably  concentrated  aliments  like  thick  bouillon.  Coincidcntly. 
the  treatment  of  paralysis  is  to  be  instituted,  strychnine  given  if 
the  urine  does  not  contain  albumin,  and  electricity  employed. 

In  the  course  of  infections  the  intestine  is  disturbed  more  than 
the  stomach.  Two  morbid  manifestations  are  especially  important : 
constipation  and  diarrhea.  For  the  treatment  of  constipation 
preference  should  be  given  to  intestinal  lavage.  If.  at  the  same 
time,  hyperthermia  is  present,  cold  enemas  may  be  prescribed,  which 
have  the  advantage  of  abstracting  heat.  In  many  cases  it  is  well 
to  give  an  enema  morning  and  evening.  The  patient  may  even  be 
instructed  to  retain  the  evening  enema.  This  procedure  has  the 
advantage  of  allowing  the  water  to  penetrate  the  organism  and.  at 
the  same  time,  softening  the  fecal  matters,  which  may  more  readily 
be  evacuated  by  the  enema  of  the  following  morning. 

We  cannot  dwell  upon  the  indications  of  the  various  kinds  of 
enemas  or  upon  the  conditions  in  which  purgatives  are  to  be 
preferred.     There  are  special  rules  for  each  infection.     It  is  well. 

53 


834  INFECTIOUS  DISEASES. 

however,  to  remember  that  a  good  many  physicians  dread  purgatives 
in  the  course  of  eruptive  fevers  and  erysipelas.  In  fact,  it  is  better 
to  prescribe  enemas  or  lavage  through  a  tube.  If  their  action  is 
found  insufficient,  a  very  mild  purgative  may  be  given.  In  this 
connection  castor  oil  gives  satisfactory  results. 

Constipation  may  be  accompanied  by  intestinal  paresis  expressed 
by  tympanites.  In  this  case  very  hot  or  very  cold  applications 
should  be  made  to  the  abdomen.  There  may  at  the  same  time  be 
introduced  into  the  rectum  a  catheter,  which  soothes  the  patient 
considerably  by  facilitating  the  expulsion  of  gases.  Constipation 
should  not  always  be  combated.  In  certain  abdominal  lesions,  in 
typhoid  appendicitis,  and  in  peritonitis  it  is  a  sort  of  salutary 
reaction,  and  is  clue  to  intestinal  immobility  which  prevents  exten- 
sion of  the  lesions.  Here  an  important  problem  faces  us:  we  must 
either  immediately  intervene  and  extirpate  or  open  the  morbid 
focus,  by  a  surgical  operation,  or  else  follow  an  expectant  course, 
and  therefore  respect  the  constipation,  and  at  times  even  increase 
it  by  means  of  opium. 

Diarrhea  is  sometimes  to  be  respected  and  even  favored  by  means 
of  purgatives.  Sometimes  it  must  be  checked.  The  treatment  is 
to  be  guided  by  an  accurate  diagnosis.  In  typhoid  fever  the  employ- 
ment of  purgatives  is  of  service,  especially  at  the  beginning  and  at 
the  end  of  the  disease.  At  the  beginning  calomel  may  be  given; 
at  the  end,  when  diarrhea  persists,  or  when  it  occurs  at  the  beginning 
of  convalescence,  attended  by  some  febrile  movement,  a  saline 
purgative  produces  excellent  effects.  The  action  of  purgatives 
during  the  stationary  period  is  more  contestable.  They  are  said  to 
increase  meteorism  and  favor  perforations.  I  believe  this  opinion 
not  to  be  well  founded,  and  think  that  in  most  cases  a  saline  pur- 
gative may  be  prescribed  every  five  or  six  days.  Moreover,  this  is 
an  excellent  means  of  accomplishing  intestinal  antisepsis.  For  the 
same  reason  a  purgative  also  succeeds  in  the  majority  of  infectious 
diarrheas.  When,  however,  the  general  state  of  the  patient  is  grave 
and  the  alvine  evacuations  are  abundant,  giving  rise  to  cold,  spasms, 
and  cyanosis,  I  believe  it  is  better  to  employ  antidiarrheal  substances, 
such  as  subnitrate  of  bismuth.  This  is  given  by  the  mouth  in  doses 
of  from  4  to  6  grams,  and,  if  necessary,  from  10  to  20  grams  may 
be  introduced  into  the  intestine  through  a  tube.  This  furnishes  a 
dressing  comparable  to  that  practised  for  the  stomach.  Bismuth 
is  generally  associated  with  some  insoluble  antiseptic,  and  the  treat- 


THEBAPEUTI08  OF  TNFEOTIOUS  DISEASES. 

tnent  is  completed  by  the  administration  of  milk  mixed  with  lime- 
water,  rice,  and  some  stimulants,  uch  s  tea  with  rum,  and  ether, 
bo  which  injections  of  camphorated  oil  may  be  added  in  grave  c 

Whether  purgatives  or  constipating  medicines  are  resorted  '<>,  it 
is  always  advisable  a1  the  same  time  to  utilize  enemai  and  still 
better  profuse  intestinal  irrigations  with  boiled  salt-water  or  anti- 
septic substances.  The  putrefied  substances  and  microbe*  are  thus 
mechanically  thrown  out. 

Gastrointestinal  disturbances  readily  involve  the  liver,  in  mosl 
cases  it  will  suffice  to  continue  the  general  treatment.  Profuse 
intestinal  irrigations  with  cold  water  a1  53.5°  or  59  I  ,  I L2  or  L5  ' 
a,s  well  as  an  absolute  milk  diel  and  cold  baths,  are  particularly 
to  be  insisted  upon.  As  ;i  more  special  medieinc  we  may  cite  calomel  \ 
a  small  dose  of  1  or  2  eg.  given  every  morning  produces  satisfactory 
results.  The  special  action  of  ether  upon  the  liver  has  already  been 
explained.  Let  us  add  the  role  of  salicylic  acid  and  its  derivatives, 
notably  salol.  This  medicine  has  the  triple  advantage  of  being 
cholagogue,  of  decreasing  the  pain  produced  by  inflammation  of 
the  biliary  passages  and  of  realizing  a  relative  antisepsis  in  these 
passages.  In  cases  of  renal  lesions  the  salicylates  are  not  well  borne. 
Hence,  benzoate  of  soda  should  be  substituted  therefor. 

Treatment  of  Renal  Disorders.  Alterations  of  the  kidney  in  the 
course  of  infections  often  embarrass  therapeutics  by  contraindicating 
the  employment  of  certain  active  medicines.  These  lesions  may  be 
treated  by  revulsion  at  the  beginning,  or  by  dry  or  scarified  cupping 
applied  to  the  lumbar  region.  If  hematuria  appears,  ergotin  or, 
still  better,  calcium  chloride,  is  given.  Then  the  oxidizing  method 
is  resorted  to ;  from  2  to  6  grams  of  benzoate  of  soda  are  prescribed. 
It  is  understood  that  the  patient  is  to  be  put  on  an  absolute  milk 
diet.  In  many  cases  satisfactory  results  will  be  obtained  by  dimin- 
ishing the  formation  of  autogenic  poisons  by  means  of  antisepsis  and 
profuse  irrigation  of  the  intestine. 

Albuminuria,  which  sets  in  during  convalescence,  is  to  be  treated 
as  during  the  stationary  period.  "When  it  becomes  chronic  the 
milk  diet  cannot  be  prolonged  indefinitely.  ^While  some  patients 
bear  it  well,  others  experience  marked  disgust  and  vomit  the  milk 
every  time  they  take  it. 

The  diet  must  then  be  modified.  Coffee  or  rice  may  be  added  to 
milk,  some  vegetables,  eggs,  and.  if  desirable,  white  meat  may  be 
permitted.    Instead  of  bread,  dry  toast  should  be  given.    In  general. 


836  IXFECTIO  US  DISEASES. 

diuretics  are  useless.  If  any  are  to  be  used,  theobromin  should  be 
prescribed.  It  is  better  to  favor  diuresis  indirectly  by  cold  enemas, 
oxidants,  and  especially  benzoate  of  soda.  In  certain  cases  tannin, 
if  it  is  well  borne  by  the  stomach,  proves  serviceable.  Stronger 
medicines  seem  to  be  contraindicated.  In  a  case  of  albuminuria 
with  a  slow  course,  consecutive  to  scarlet  fever,  the  author  prescribed 
one  drop  of  tincture  of  cantharides.  This  little  dose  sufficed,  how- 
ever, to  produce  hematuria  and  aggravate  the  previous  symptoms. 


CHAPTER    XXIV. 
HYGIEN'IO  AND  PROPHYLAXIS  OF  ENFECTTOUS  DISEASES. 

[ndividual  Hygiene,     Isolation  of  the  Patient.     Precaution     to  be  Taken  b 

Waiting  upon  the  Patient.  Bygiene  of  the  Sick-room.  l»i  infection  of  thi  Bedding 
and  Linen.  Sterilization  and  Destruction  of  Secretions,  Excretion  ,and  Squamata 
Cleanliness.     Alimentation.     Beverages.     Hygiene  of  ConvaL  Social   Hj 

giene.     Quarantine.      Isolal  ion  Hospitals.     Transfer  of  Contagiou    '  B  I  Declara- 

tion of  Contagious   Diseases.     Municipal   Service  of    Disinfection.      Vaccination. 

Variolization.  Syphilization.  Vaccine.  Personal  Statistics  Showing  » lie  Lnflui 
of  Vaccine  upon  the  Course  of  Variola.  Vaccination  by  Mean  of  Atten  I 
Viruses.  Anthrax  Vaccine.  Vaccination  against  Hydrophobni.  Vaccination  by 
Moans  of  Sterilized  Cultures.  Attempts  at  Immunization  ;igain-t  Cholera  and 
Typhoid  Fever.  Prophylactic  Injections  of  Serum.  Application  of  the  Serum 
Method  to  the  Prophylaxis  of  Diphtheria,  Puerperal  Fever,  Tetanus,  and  Bubonic 
Plague.    Conclusions. 

Individual  Hygiene. 

Hygiene  of  the  Sick  Room.  The  therapeutics  of  infectious  dis- 
eases, notwithstanding  its  considerable  interest,  is  perhaps  less  impor- 
tant than  the  hygienic  measures  which  must  be  observed  with  refer- 
ence to  the  patient  and  those  surrounding  him. 

In  the  case  of  a  contagious  disease,  perfect  isolation  of  the  patient 
is  the  first  requirement  to  be  met.  To  this  end  it  is  necessary  to 
have  two  rooms  at  one's  disposal,  one  in  which  the  patient  will  lie; 
another,  contiguous  thereto,  which  will  serve  for  disinfection  of  per- 
sons who  have  approached  the  patient  and  the  objects  which  have 
come  in  contact  with  him.  In  certain  instances  it  is  preferable  to 
have  a  suite  of  three  rooms,  two  of  which  will  serve  the  patient,  one 
during  the  day,  the  other  during  the  night.  The  number  of  persons 
charged  with  the  care  of  the  patient  should  be  at  least  two,  and  it 
is  indispensable  that  these  persons  should  have  no  other  occupation 
and  fulfil  with  accuracy  the  prophylactic  measures  indicated  to  them. 

Before  entering  the  room  of  the  patient  the  visitor  should  put  on 
a  blouse,  and  it  is  well  to  protect  the  hair  by  means  of  a  cap,  and  to 
change  the  shoes.  If  the  last-named  precaution  is  not  taken,  it  will 
be  necessary  to  spread  in  the  disinfection  room  a  crash  of  several 
thicknesses,  which  has  been  sprinkled  with  a  2 :  1000  solution  of 
corrosive  sublimate,  on  which  the  shoes  should  be  rubbed  on  passing 


838  IXFECTIO  US  DISEASES. 

out  oi  the 1  mtient  s  room.  Then  the  face  and  hands  should  be  washed 
with  a  1 :  2000  solution  of  corrosive  sublimate  or  1 :  1000  solution  of 
oxycyanide  of  mercury;  if  the  person  wears  a  beard  it  is  indispen- 
sable to  cleanse  it  well  with  the  same  fluids.  Persons  waiting  upon 
the  patient  should  never  eat  or  drink  in  his  room.  The  meals  should 
be  taken  in  another  room  after  having  changed  the  clothing  and 
disinfected  the  hands  and  face.  They  should  not  carry  their  hands 
to  their  face  without  being  disinfected,  and  the  handkerchiefs  which 
they  may  have  to  use  in  the  patient's  room  should  not  be  used  out- 
side. It  is  also  indispensable  for  a  parent  to  abandon  the  unwise 
habit  of  kissing  the  patient:  they  should  avoid  every  unnecessary 
contact  with  the  patient. 

The  sick  room  should  be  large  and  well  ventilated,  with  southern 
or  eastern  exposure.  The  windows  should  be  furnished  with  Venetian 
blinds,  which  are  to  be  kept  closed  in  certain  infectious  diseases,  such 
as  measles,  variola,  and  sometimes  erysipelas.  The  red  glasses  advo- 
cated by  Finsen  for  the  treatment  of  variola,  and  at  times  employed 
in  measles,  do  not  seem  to  be  useful.  Red  light  often  exerts  a  too 
intense  excitation  upon  the  nervous  system,  while  green  light  seems 
to  be  better  borne.  The  hangings  of  the  room  should  be  removed, 
as  well  as  all  useless  objects  and  curtains.  The  bed  of  the  patient 
should  be  placed  in  the  middle  of  the  room,  or  at  least  far  from  the 
walls,  so  as  to  be  approached  from  any  side.  There  should  be,  espe- 
cially in  cases  of  obese  patients,  some  contrivance  designed  to  enable 
the  nurses  to  raise  the  patient  easily  for  cleansing  without  tiring 
him.  If  the  skin  shows  a  tendency  to  develop  bed-sores,  the  bed- 
clothes should  be  sprinkled  with  talcum  or  cinchona  powder,  and 
pneumatic  rings  or  water  cushions  should  be  used. 

When  possible  two  beds  should  be  placed,  with  a  bath-tub  between 
the  two.  When  the  patient  has  taken  a  bath  he  should  be  put  in 
the  second  bed  and,  while  he  is  resting  there,  the  other  bed  should 
be  aired  and  properly  arranged.  In  this  manner  after  each  bath  the 
patient  may  lie  down  in  a  comfortable  bed.  The  physician  should 
pay  particular  attention  to  the  ventilation  of  the  room.  In  summer 
the  windows  may  be  left  open  for  the  greater  part  of  the  day.  During 
the  night  the  window  of  the  adjoining  room  is  to  be  left  open,  and 
a  screen  should  be  placed  so  as  to  protect  the  patient  from  the 
draught  of  cold  air.  In  winter  the  ventilation  of  the  room  should 
be  assured  by  means  of  an  open  fireplace,  where  a  fire  should  be  kept 
up  night  and  day.     For  ventilating  the  room   the  window  of   the 


HYGIENE  ANI>  PR0PHYLAXI8  OF  INFECTIOUS  DI8EA8E8.    839 

adjoining  room  should  be  opened,    [f  h  i    very  cold,  the  latter  room 
must  also  be  heated ;  while  the  window  is  open  the  door  between  the 
two  rooms  should  be  kepi  closed.    The  temperature  of  the  sick-room 
should  not,  he  very  high;  it  should  be  kepi  between  61°  and  64°  I 
(16°  and  L8°  0.). 

Cleansing  and  Disinfection   of   the  Room   and  Objects;    Sterilization  of 

Morbid  Products.  'The  cleansing  of  the  room  hould  not  be  made  by 
sweeping,  which  raises  dust,  hut  by  means  of  a  mop  wel  with  .'i  solu- 
tion of  corrosive  sublimate. 

According  to  the  disease  treated,  the  patienl  may  be  permitted  to 
riso  to  attend  to  his  natural  wants,  or  the  bed-pan  may  be  employed. 
This  measure  is  indispensable  in  typhoid  fever.  The  dejecta  musl 
always  be  disinfected  before  they  are  disposed  of.  A  2:  L000  solu- 
tion of  corrosive  sublimate,  or  a  50;  L000  solution  of  copper  sulphate, 
or  lime-water,  should  he  poured  into  the  bed-pan.  The  mine  should 
be  collected  in  the  adjoining  room,  and  after  the  amount  voided  in 
twenty-four  hours  is  measured,  it  should  be  disposed  of.  In  certain 
cases,  however,  it  is  advisable  to  disinfect  the  urine.  The  urine  in 
hemorrhagic  variola  and  thai  of  typhoid  patients,  when  they  contain 
albumin  and  the  germs  of  the  disease,  are  so  to  be  treated.  The 
various  discharges  and  secretions  are  to  be  taken  upon  absorbent 
cotton  and  thrown  into  the  fire.  The  sputa  must  be  disinfected  by 
means  of  antiseptics  or  boiling.  If  there  is  desquamation,  the 
squamata  that  fall  in  the  bed-clothes  should  be  burned.  If  any  should 
fall  on  the  floor,  they  should  be  picked  up  by  means  of  a  wet  cloth. 
The  patient  should  have  exclusively  his  own  eating  utensils.  These 
should  be  cleansed  in  the  adjoining  room,  first  plunging  them  into 
boiling  water.  The  instruments  serving  for  the  usual  explorations, 
such  as  the  tongue  depressor  or  the  spoon  substituted  for  it  in 
examining  the  throat,  should  also  be  sterilized.  In  our  wards  we  em- 
ploy glass  tongue  depressors,  which  are  very  easily  sterilized.  Of 
course,  the  various  canulas,  catheters,  as  well  as  thermometers, 
should  also  be  disinfected.  It  is  advisable  to  immerse  all  the  linen 
of  the  patient  in  an  antiseptic  fluid,  thus  preventing  the  possible 
dissemination  of  dried  products  and  squamata  until  they  are  sent 
away  for  disinfection.     A  solution  of  lysol  serves  this  purpose  well. 

During  the  course  of  the  disease,  and  especially  during  convales- 
cence, the  patient  often  asks  to  write.  If  his  desire  is  to  be  complied 
with,  the  paper  should  be  sterilized  by  means  of  sulphur  Or  formol 
vapor.    "When  he  begins  to  get  up  he  must  put  on  clothing  which 


840  INFECTIOUS  DISEASES. 

may  be  disinfected  afterward.  Finally,  after  a  certain  period  of  time 
he  may  be  permitted  to  resume  his  ordinary  occupation.  It  is  diffi- 
cult to  determine  at  what  moment  a  convalescent  individual  is  no 
longer  contagious.  The  period  of  isolation  has  been  fixed  at  sixteen 
days  in  measles,  varicella,  and  mumps,  and  at  fortjr  days  in  scarlet 
fever  and  variola.  These  averages  are  acceptable.  The  author 
believes,  however,  that  the  quarantine  in  cases  of  measles  may,  with- 
out any  inconvenience,  be  reduced.  For  varicella  and  variola,  isola- 
tion may  be  abridged  in  mild  cases,  when  there  are  only  a  few  eruptive 
elements  and  the  desquamation  is  complete.  On  the  other  hand, 
after  a  confluent  variola,  if  the  crusts  persist  at  the  end  of  forty  days, 
the  danger  of  contagion  has  not  yet  disappeared,  and  isolation  must, 
therefore,  be  prolonged. 

In  case  of  diphtheria,  cultivation  is  often  resorted  to;  as  long  as 
Loeffler's  bacillus  is  found  isolation  is  to  be  maintained.  If  at  the 
end  of  three  weeks  the  microbe  has  disappeared,  an  inoculation  into 
the  guinea-pig  is  advisable.  These  precepts  are  perhaps  good,  but 
they  have  the  great  inconvenience  of  not  being  sufficiently  practical. 
One  may,  therefore,  be  contented  with  isolating  the  patient  for  three 
weeks,  then  he  should  be  advised  to  practise  for  at  least  a  month, 
morning  and  evening,  cleansing  of  the  mouth  by  means  of  boiled 
water  to  which  thymol  is  added  in  the  proportion  of  1 :  1000. 

When  it  is  thought  that  the  patient  needs  no  longer  to  be  isolated, 
he  must  be  given  in  the  adjoining  room  a  last  antiseptic  bath  with 
corrosive  sublimate  or  naphtol.  If  possible,  his  hair  should  be  cut 
very  close;  at  all  events,  complete  cleansing  of  the  scalp  with  soap 
and  then  with  some  antiseptic  water  should  be  made,  this  to  be 
followed  by  rubbing  with  alcohol.  After  the  bath,  the  patient  should 
put  on  clean  clothing,  and  leave  definitely  the  rooms  in  which  he  has 
been  treated.  These  rooms  are  then  to  be  disinfected  by  means  of 
hot  corrosive  sublimate  solutions  or  vapors  of  sulphur  or  formal- 
dehyde. In  our  wards,  after  cleansing  with  corrosive  sublimate,  we 
burn  30  grams  of  sulphur  per  cubic  metre  of  space.  The  locality  is 
kept  closed  for  twenty-four  hours.  Moreover,  all  objects  of  little 
value  which  have  been  used  by  the  patient,  such  as  toys  and  books, 
should  be  burned.  It  is  understood  that  domestic  animals  must  not 
be  allowed  to  enter  the  patient's  room,  for  their  hair  becomes  charged 
with  infective  products,  which  may  then  be  easily  disseminated. 

Hygiene  of  the  Sick.  During  the  course  of  infection  cleanliness 
of  the  patient  must  be  constantly  attended  to.    If  there  is  no  special 


iiy<ui<;ni<;  and  PROPHYLAXIS  OF  INFECTIOUS  DISEASES.    h\\ 

reason  for  the  employment  of  balneotherapy,  it  i  advi  able, 
hygienic  measure,  fco  give  the  patienl  s  lukewarm  bath  of  fifteen  or 
twenty  minutes  every  day  or  every  other  day.  Alter  each  meal  the 
mouth  of  the  patient  musl  be  cleansed.  After  each  injection  the 
urinary  organs  and  anus  should  be  cleansed.  Likewise,  the  mouth 
is  to  be  cleansed  every  morning  with  Vichy  water  or  borated  solution, 
the  teeth  brushed,  and  a  small  amounl  of  mentholated  pomatum 

introduced  into  the  nostrils;  the  CUtaneoUS  abrasiOM  nui-t  he  di< 

and,  in  case  of  desquamation,  a  little  vaselin  should  he  3preadupon 

the  skin.  It  is  also  very  useful  to  prescribe  daily  one  or  two  enemas 
in  order  to  cleanse  the  lower  portion  of  the  intestine.  A  little 
caution  which  should  not  he  overlooked  ;it  the  beginning  of  infectious 
diseases  is  to  remove  the  jewels,  rings,  and  ear-rings  of  the  patient. 
In  case  of  erysipelas,  ear-rings  may  give  rise  to  ;i  sphacelus  in  the 
inflamed  lobe.  In  several  cases  the  author  has  seen  the  finders- 
swollen  under  the  influence  of  the  variola  erupt  ion  and  so  strangu- 
lated by  rings  that  the  cutting  of  those  ornaments  became  a  diffi- 
cult matter. 

Alimentation.  As  has  already  been  stated,  patients  must  be  fed 
during  infections.  As  a  general  rule,  they  should  be  given  milk, 
bouillon,  and  a  certain  amount  of  beverage,  but  care  should  be  taken 
to  give  a  very  small  amount  of  liquid  each  time.  The  best  practise 
is  to  give  a  glass  or  a  glass  and  a  half  of  milk  every  hour.  Vichy, 
lime-water,  or  pancreatin  may  be  added  to  the  milk.  If  this  nourish- 
ment  is  not  kindly  borne,  a  little  beer-yeast  ma}-  be  given,  or  the 
milk  may  be  replaced  by  some  other  substitute.  (See  footnote, 
page  832.)  The  amount  of  milk  varies  according  to  the  case:  it  may 
be  said  to  be  for  an  adult  two  quarts  (two  litres)  a  day.  In  cases 
of  scarlatina  milk  must  be  the  only  aliment :  no  bouillon  is  to  be 
permitted,  but  some  beverages  sweetened  with  syrup  of  currant  or 
pomegranate,  or  sweet  barley-water.  The  milk  diet  being  absolute, 
three  quarts  of  it  must  be  given  daily  for  twenty  days.  At  the  end 
of  this  time  if  the  urine  contains  no  albumin  a  more  substantia] 
alimentation  may  be  resumed,  such  as  bouillon,  rice,  creams  of  vege- 
tables, eggs,  and,  four  or  five  days  after,  even  meat  may  be  given. 
Should  some  albumin  appear  in  the  urine,  the  absolute  milk  diet 
should  again  be  instituted,  which  is  to  be  discontinued  eight  or  ten 
days  after  the  disappearance  of  albuminuria. 

In  most  other  diseases,  including  typhoid  fever,  two  quarts  two 
litres)  of  milk  and  one  quart  (one  litre)  of  bouillon  are  generally 


842  IXFECTIOUS  DISEASES. 

given.  Dr.  Robin  also  prescribed  beef-tea  prepared  by  heating  small 
pieces  of  meat  with  one  quart  (one  litre)  of  bouillon  in  a  double 
boiler.  In  order  not  to  coagulate  the  albumins,  care  is  to  be  taken 
not  to  raise  the  temperature  above  140°  F.  (60°  C).  Bouillon  has 
the  advantage  of  acting  as  a  peptogen  and,  at  the  same  time,  intro- 
ducing into  the  organism  salts  to  compensate  for  the  loss  of  mineral 
matters.  The  amount  of  salts  is  from  eight  to  ten  grams  in  a  litre 
(1000  c.cm.).  Vegetable  infusions  may  likewise  be  utilized.  A  very 
good  preparation  consists  in  mixing  one  part  of  barley-water  with 
two  of  milk;  this  is  preferably  sweetened  with  honey.  This  mixture 
is  often  very  well  borne  by  those  who  do  not  like  milk.  When,  how- 
ever, the  repugnance  for  milk,  experienced  by  some  patients,  cannot 
be  overcome,  one  is  compelled  to  resort  to  some  other  alimentation. 
Bouillon  and  also  bouillon  with  an  egg  added  to  it  (lait  de  poule). 
It  is  well  to  complete  the  diet  by  a  small  amount  of  alcoholic  bever- 
ages: according  to  the  case,  vinous  lemonades,  Malaga  or  Bagnols 
wine,  and  Todd's  potion.  Coffee  may  also  be  permitted  in  the  pro- 
portion of  10  grams  for  200  grams  of  water. 

The  diet  above  indicated  has  not  seemed  sufficient  to  certain  physi- 
cians who  at  present  nourish  their  patients  substantially.  As  a 
matter  of  fact,  three  or  four  quarts  (three  to  four  litres)  of  milk  must 
be  given  in  order  to  meet  the  wants  of  the  economy.  So  great  a 
quantity  is  too  much  for  some  patients  to  bear.  Moreover,  milk 
contains  an  inadequate  proportion  of  albumin  and  carbohydrates, 
and  an  excess  of  fat.  It  is  necessary  to  increase  the  administration 
of  nitrogenous  aliments.  This  is  what  was  done  by  the  addition  of 
bouillon.  At  present  several  Russian  physicians  go  farther.  Dr.  Va- 
quez,  who  has  tried  the  new  method  in  typhoid  fever,  advises  a  cup 
of  milk  every  other  hour  only;  at  8  a.m.  he  gives,  instead  of  milk, 
cafe  au  lait  or  a  soup  with  milk,  and  some  flour  or  rice.  At  noon 
and  at  6  p.m.  milk  is  replaced  by  a  meal  composed  of  some  soup  or 
a  bouillon  containing  the  yolk  of  an  egg  and  a  small  cup  of  meat 
jelly,  or  fresh  meat  juice.  At  the  end  of  the  disease,  raw  meat, 
preferably  chopped  mutton,  is  given.  Two  or  three  days  after  the 
fall  of  the  fever,  creams  of  vegetables  are  given,  and  toward  the 
eighth  day  eggs,  dry  toast,  and  stewed  fruits  are  allowed. 

By  thus  nourishing  the  patient,  we  succeed  in  preventing  adynamic 
manifestations  and  abridging  considerably  the  period  of  convales- 
cence. Intestinal  disturbances,  perforations,  hemorrhages,  and  con- 
sequent relapses  were  feared;  according  to  published  observations, 


IIYUIHNH  AND  I'JiOI'U  YLAXIS  OF  INFECTIOUS  DI8EA8ES.    843 

however,  this  apprehension  is  not  well  founded.  The  feeding  having 
been  continued  during  the  entire  course  of  the  disea  e,  itt  incri 
at  the  time  of  convalescence  gives  rise  to  nodi  order.  On  the  con- 
trary,  Lt  is  known  how  frequenl  are  relapse*  in  those  ca  <•  which  are 
subjected  to  milk  diet,  when  the  patient  are  too  oon  permitted  to 
take  substantia]  food. 

Barring  the  case  of  typhoid  fever,  the  author  thinks  thai  in  .-ill 
oilier  infections  excepl  scarlatina  ;i  sufficiently  plentiful  and  varied 
alimentation  may  be  allowed  without  any  fear.  The  author  gives 
milk,  bouillon,  eggs  with  soups  and  particularly  hurley  and  rice  soup, 
according  as  (here  is  tendency  to  constipation  or  to  diarrhea.  This 
diet  seems  to  him  especially  importanl  in  variola.  Mi-  experiments 
demonstrated  that  abundanl  alimentation  often  enables  animals  to 
resist  the  inoculation  of  variola.  In  some  cases,  however,  we  may 
have  some  difficulty  in  overcoming  the  resistance  of  patients  whose 
throats  are  covered  with  pustules  and  who  suffer  when  they  swallow 
food.  In  such  cases,  gargling  with  an  infusion  of  cocoa  Leaves  should 
be  prescribed  or  the  throat  painted  with  a  cocaine  solution  before  each 
meal.  Should  these  methods  fail,  the  patient  should  he  fed  by  means 
of  a  tube  introduced  through  the  nose.  Should  albumin  appear  in 
the  urine  the  patient  should  be  put  on  milk  diet,  eggs,  and  rice.  The 
same  alimentation,  with  the  same  restrictions,  is  to  be  employed  in 
diphtheria.  During  convalescence  the  patient  should  be  given  more 
liberal  nourishment.  If  there  are  renal  complications  and  albumin 
in  the  urine,  the  diet  should  be  limited  to  milk,  coffee,  raw  eggs,  and 
rice,  a  small  amount  of  farinaceous  food  in  the  form  of  puree  and 
stewed  fruits.  No  meat  is  given,  and  instead  of  bread,  dry  toast. 
If  paralysis  of  the  palate  develops,  notably  as  a  result  of  diphtheria, 
purees  are  the  aliments  most  readily  accepted  by  the  patient.  He 
must  be  advised  to  swallow  the  liquids  with  the  head  thrown  back, 
and  to  drink  very  slowly,  lying  on  his  back  so  as  to  cause  the  fluids 
to  flowT  according  to  the  laws  of  gravitation. 

In  conjunction  with  the  aliments  a  certain  amount  of  beveragi  -  - 
to  be  allowed.  The  thirst  experienced  by  the  patient  clearly  in<  licates 
that  his  organism  wants  water.  Slight  infusions,  sweetened,  should 
be  given.  Milk  not  being  sufficiently  rich  in  carbohydrates,  it  is  well 
to  put  sugar  in  the  beverages.  For  the  same  purpose  boiled  lemon- 
ades, vinous  lemonade,  and  some  Vichy  may  be  given  with  a  little 
syrup.  If  the  stomach  does  not  tolerate  fluids  well,  the  beverages 
should  be  replaced  by  enemas,  which  the  patient  must  retain.     In 


844  INFECTIOUS  DISEASES. 

such  cases  subcutaneous  injections  of  artificial  serum  yield  gratifying 
results. 

Hygiene  of  Convalescents.  During  convalescence,  diet  is  to 
receive  special  attention.  Nourishment  must  be  progressively  in- 
creased and  the  patient  gradually  allowed  to  return  to  his  habits  in 
the  matter  of  eating,  but  the  digestive  functions  must  be  carefully 
watched.  If  flatulence,  slow  digestion,  hypochlorhydria  or  hyper- 
chlorhydria  occur, the  various  classical  treatments  of  dyspepsia  should 
be  employed.  The  intestinal  function  also  requires  attention.  Exag- 
geration of  gastrointestinal  putrefactions,  constipation,  and  diarrhea 
and  mucomembranous  enteritis  are  not  rare  in  consequence  of  infec- 
tions. At  all  events,  the  convalescent  must  be  instructed  to  eat 
slowly  and  masticate  well,  and  take  at  least  four  meals  daily.  After 
each  meal  he  must  take  a  rest  for  an  hour,  either  sitting  or  lounging, 
and  a  little  more  covered  than  usual,  since  a  convalescent  is  more 
sensitive  to  cold  than  normal  subjects.  It  is,  therefore,  advisable  to 
give  them  warmer  clothing  and  to  have  their  room  at  a  higher 
temperature  than  usual.  The  room  must  be  well  ventilated:  in 
summer  the  windows  should  always  be  kept  open,  and  during  the 
night  those  of  the  adjoining  room.  Exercise  must  be  moderate  and 
progressive.  It  will  be  useful  for  a  certain  length  of  time  to  continue 
to  take  the  rectal  temperature,  at  least  in  the  evening.  An  eleva- 
tion in  the  temperature  often  announces  that  alimentation  is  not 
well  borne  or  that  exercise  has  caused  too  much  fatigue.  When 
convalescence  is  well  established  it  is  desired,  whenever  possible,  to 
send  the  patient  to  a  summer  or  winter  resort,  according  to  the 
season. 

The  author  cannot  too  much  emphasize  the  necessity  of  devoting 
continued  attention  to  the  toilet.  A  convalescent  should  take 
slightly  tonic  sulphur  or  salted  baths.  He  must  rub  his  body  every 
morning  for  five  minutes  with  a  Turkish  towel  or  rough  flannel  wet 
with  some  alcoholic  preparation,  for  example,  lavender  brandy.  In 
order  to  be  able  to  judge  the  efficacy  of  these  measures,  it  is  advisable 
to  weigh  the  convalescent  once  a  week  and  examine  his  strength  by 
means  of  the  dynamometer.  If  the  functions  are  not  re-established 
with  gratifying  rapidity,  bitters  should  be  prescribed  in  case  of  ano- 
rexia, and  tonics,  such  as  lecithin,  in  case  of  weakness.  In  such  cases 
subcutaneous  injections  of  artificial  serum  are  also  practised.  Finally, 
the  alimentary  method  may  be  modified,  and  raw  meat,  for  instance, 
may  be  recommended. 


JIYaiKNK  and  morn  y LA x is  OF  INFECTIOUS  DISEASES.    845 

Social  Hygiene. 

The  advice  above  presented  with  reference  to  the  hygienic  tri 
merit  and  isolation  of  patients  is  not  alwa;.  o!  application.     In 

order  to  isolate  a  contagious  case,  two  person  bould  be  a  igned  to 
his  service  exclusively.  Among  the  poorer  cla  i  when 
individuals  occupy  one  room,  isolation  is  impossible.  Wha1  further 
aggravates  the  situation  is  thai  patients  are  attended  by  parents, 
friends,  an<l  sometimes  Hie  janitor,  and  thai  personf  thu  approach 
ing  the  patient  return  to  their  occupations  without  taking  any  anti- 
septic precautions.  Hence,  epidemics  ravage  the  crowded  sections 
of  cities  and  make  certain  tenement-houses  centre;-  of  infection. 

While  certain  laws  have  been  promulgated  for  preventing  the 
importation  of  epidemics  from  foreign  countries,  hardly  any  meas- 
ures have  been  taken  to  insure  isolation  of  contagious  patients  in 
domestic  epidemics.  The  only  progress  up  to  the  present  time  real- 
ized in  France  has  been  the  establishment  of  services  of  disinfection, 
of  vaccination  at  home,  and  of  transportation  of  contagious  patients 
in  special  vehicles  and  urban  ambulances.  It  is,  of  course,  out  of  the 
question  to  isolate  all  contagious  cases.  Only  those  individuals  who 
suffer  from  acute  infections  may  be  isolated  in  appropriate  institu- 
tions. When  the  question  is  one  of  chronic  infection,  such  as  tuber- 
culosis, other  measures  are  applicable.  A  fight  against  the  latter 
disease  has  been  undertaken  with  gratifying  results.  The  public  is 
warned  by  means  of  placards  in  public  establishments,  surface  car.-, 
wagons,  not  to  spit  upon  the  floors,  and  in  a  good  many  establish- 
ments hygienic  cuspidors  have  been  placed;  public  lectures  and  popu- 
lar books  on  tuberculosis  have  been  published.  Moreover, sanitariums 
and  rural  colonies  have  been  created.  There  are  already  more  than 
a  hundred  of  these  in  France  alone. 

Declaration  of  Contagious  Diseases;  Disinfection  by  Officers  of 
the  Board  of  Health;  Transportation  of  Patients.  The  law  i  if  Novem- 
ber 30,  1892,  obliges  every  physician,  under  penalty  of  the  law.  to 
pay  a  fine  of  from  fifty  to  two  hundred  francs  to  declare  to  the  public 
authorities  the  cases  of  contagious  diseases  coming  under  his  obser- 
vation in  the  course  of  his  practice.  The  present  list  includes  the 
following  twelve  diseases:  typhoid  fever,  typhus  fever,  variola  and 
varioloid,  scarlatina,  diphtheria,  sudor  anglicus,  cholera  and  choleri- 
form  maladies,  bubonic  plague,  yellow  fever,  dysentery,  puerperal 
infections,  and  ophthalmia  of  the  newborn.     Certain  milder  infec- 


846  INFECTIOUS  DISEASES. 

tions,  such  as  mumps,  varicella,  and  whooping-cough,  have  been  left 
out,  as  also  others  that  are  not  very  contagious,  such  as  erysipelas, 
or  are  contagious  for  a  short  time  only,  such  as  measles.  It  would, 
however,  be  advisable  to  add  pneumonia  to  the  list. 

When  patients  ask  to  be  treated  outside  of  their  homes  they  are 
transported  in  particular  vehicles  and  their  residence  is  disinfected 
free  of  charge — these  are  gratifying  advances.  It  seems  to  the 
author,  however,  that  it  is  high  time  to  take  serious  prophylactic 
measures,  and  thus  complete  the  law  of  1892.  It  is  necessary  to 
determine  in  what  diseases  isolation  shall  be  compulsory.  When  the 
residence  of  the  patient  does  not  permit  isolation  under  sanitary 
precautions,  such  cases  should  be  transported  to  a  special  hospital. 
It  is  also  necessary  to  determine  the  average  duration  of  contagious- 
ness and  engage  the  civic  responsibility  of  every  individual  who 
places  himself  in  a  position  to  directly  or  indirectly  contaminate 
his  fellow  citizens. 

Finally,  there  remains  a  last  question.  There  is  a  fearful  disease 
against  which  we  possess  an  infallible  prophylactic  means,  namely, 
variola.  The  measures  indicated  above  should  be  completed  by  a 
law  bearing  on  compulsory  vaccination.  We  are  thus  led  to  the 
study  of  a  question  which,  from  a  sociological  standpoint,  is  of  prime 
importance,  that  is  the  question  of  vaccination. 

Vaccinations.  The  term  vaccinia,  which  signifies  disease  of  the 
cow,  primarily  designated  an  eruptive  infection  afflicting  cows  and 
horses,  which  is  transmissible  to  various  animal  species  and  notably 
to  man,  confers  upon  the  latter  immunity  from  vaccinia  and 
variola.  Vaccination  is  the  inoculation  into  man,  with  a  prophy- 
lactic view,  of  the  disease  of  the  cow.  The  sense  of  the  term  has 
gradually  been  broadened  considerably,  and  to-day  under  the  name 
vaccination  are  included  the  various  methods  which  are  capable  of 
conferring  immunity  against  a  future  infection  or  preventing  the 
development  of  a  disease  while  at  its  stage  of  incubation. 

At  present  we  are  acquainted  with  a  number  of  methods  which 
enable  us  to  confer  immunity  and  thus  practise  preventive  medi- 
cation. For  the  convenience  of  description  the  principal  procedures 
advocated  may  be  grouped  under  six  classes: 

1.  We  may  inoculate  the  disease  against  which  we  wish  to  preserve 
the  individual.  This  method,  the  most  ancient  of  all,  has  been 
utilized  against  variola.  It  was  proposed  by  Auzias-Turenne  against 
syphilis.    It  is  still  employed  in  veterinary  medicine  for  protecting 


HYGIENE  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES.     -  17 

animals  from  symptomatic  anthrax,  murr  (fool  and  mouth  disei 
and  peripneumonia. 

"2.  A  benign  disease  may  be  inoculated  to  pre  erve  the   ndividual 
from  a  grave  disease.    Such  is  the  case  with  vaccinia,  which    i 
to  be  a  disease  different  from  variola  and  pre  erve    the  individual 
from  the  latter. 

In  (he  two  preceding  cases  .'i  non  modified  virus  i-  introduced 
into  the  organism. 

',\.  The  third  method  consists  in  inoculating  a  vim.-  which  bas 
boon  partially  freed  from  its  noxious  properties.  This  method  is 
often  designated  Pasteurian  vaccination.  It  i-  employed  ae  a  pro- 
phylactic in  animals,  notably  againsl  anthrax,  and  \\ith  ■•'  thera- 
peutic view  in  man,  especially  againsl  hydrophobia. 

4.  Instead  of  inoculating  attenuated  although  still  living  microbes, 
the  products  secreted  by  bacteria  may  be  employed,  as  is  often  done 
in  laboratories.  Such  is  the  method  initiated  by  Ferrari  againsl 
cholera,  and  which  is  utilized  by  Ilaffkin  against  bubonic  plague. 

5.  Having  remarked  the  analogy  existing  between  the  action  of 
certain  toxins  and  that  of  certain  substances  of  vegetable  origin, 
Peyraud  endeavored  to  learn  whether  some  poisons  of  a  more  or 
less  definite  chemical  character  could  not  preserve  from  infections. 
These  chemical  vaccinations  might  bo  utilized  against  tetanus  and 
hydrophobia.  Strychnine  is  expected  to  confer  immunity  from  the 
former  of  these  two  infections,  and  the  essence  of  tansy  from  the 
latter. 

6.  Finally,  therapeutic  serums  are  not  merely  curative:  they  may 
be  utilized  as  preventives.  Antidiphtheritic,  antitetanic,  anti- 
streptococcic, and  antibubonic  serums  have  been  employed  for  this 
purpose. 

Immunization  by  Means  of  Strong  Viruses.  "\  ARIOLIZATION  AND 
Svphilizatiox.  Variolization  is  a  very  ancient  method  which  has 
come  to  us  from  China.  It  was  first  introduced  into  Persia,  thence 
into  Turkey,  in  1673,  by  E.  Timoni  and  J.  Pylarini.  In  1721  the 
wife  of  the  British  ambassador  in  Constantinople,  Lad}-  Montague. 
who  saw  the  fairly  satisfactory  results  obtained  by  this  procedure, 
brought  it  to  the  knowledge  of  her  friends  on  her  return  to  London. 
The  new  method  spread  quite  rapidly,  and  was  very  happily  modified 
by  two  Scotch  farmers,  Suttey  brothers,  who  invented  subcutaneous 
inoculations.  Inoculation  of  the  variolar  virus  commonly  induces 
a  benign  disease.     It  is  not  difficult  to  comprehend  the  difference 


848  iyFECTIO  US  DISEASES. 

which  separates  the  evolution  of  the  inoculated  disease  from  that 
of  the  spontaneous  malady.  In  the  case  of  inoculation  the  patho- 
genic agent  is  introduced  beneath  the  skin — i.  e.,  into  a  region  that 
is  not  favorable  to  its  development.  As  a  matter  of  fact,  the  spon- 
taneous disease  probably  results  from  inoculation  into  the  respiratory 
apparatus.  The  result  is  analogous  to  that  observed  when  the  virus 
of  tuberculosis  or  even  of  glanders  is  introduced  beneath  the  skin ; 
the  infection  is  exhausted  in  local  symptoms,  and  with  difficulty 
invades  the  entire  economy.  On  the  other  hand,  immunizing  inocu- 
lation is  practised  upon  normal  individuals  who  are  in  good  health 
and  in  nowise  predisposed  to  infection.  On  the  contrary,  the 
spontaneous  disease  attacks  debilitated  individuals,  or  at  least  those 
whose  resistance  is  weakened  by  a  series  of  predisposing  or  auxiliary 
causes.  Variolization,  however,  is  not  always  harmless;  the  inocu- 
lated organism  may  be  found  in  such  conditions  of  predisposition  as 
to  favor  generalization  of  the  infection,  which  may  then  assume  a 
serious  course,  and  at  times  terminate  fatally.  Moreover,  even  if  the 
inoculated  individual  resists,  the  few  pustules  which  develop  may 
become  the  means  of  propagation  of  the  infection,  and  thus  constitute 
a  danger  for  others.  A  starting  point  of  an  epidemic  may  thus  be 
created. 

Although  variolization  has  rendered  some  service,  it  must  be 
abandoned  at  present  and  give  way  to  vaccination.  Can  the  method 
be  applied  to  other  diseases?  We  have  above  alluded  to  syphilization. 
As  is  known,  Auzias-Turenne  endeavored,  in  1844,  to  accomplish 
with  regard  to  syphilis  what  was  done  for  smallpox.  At  that  time, 
however,  soft  chancre  was  not  differentiated  from  the  indurated 
variety.  The  virus  of  the  soft  chancre  was  inoculated.  Auzias- 
Turenne  injected  pus  and  repeated  the  inoculations.  There  came 
a  moment  when  at  least  a  relative  immunity  was  acquired :  the  soft 
chancre  no  longer  developed  or  appeared  under  a  mild  form,  and  the 
author  believed  he  had  thus  conferred  immunity  against  syphilis. 
When,  in  the  Congress  of  1867,  it  was  pointed  out  to  him  that  he 
had  inoculated  a  virus  different  from  that  of  syphilis,  Auzias- 
Turenne  modified  his  theory.  On  the  ground  of  the  immunity 
conferred  by  vaccine  against  variola,  he  argued  that  the  virus  of 
soft  chancre  may  immunize  an  individual  or  cure  him.  Experiments 
failed  to  verify  this  conception.  Individuals  who  were  inoculated 
a  great  number  of  times — 287  times  in  a  case  of  Danielssen — con- 
tracted the  indurated  chancre  when  the  syphilitic  virus  was  em- 


"HYGIENE  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES.    .-  r.i 

ployed.  Sperino's  idea  of  combating  syphilis  by  mean  of  repeated 
inoculations  with  the  virus  of  both  soft  and  indurated  chancri 
not  yielded  any  better  results.  The  method  was  therefore  aban- 
doned. Us  failure  should  not,  however,  lead  tu  to  overlook  the 
fact  that  Auzias-Turenne  pursued  interesting  experiments  on 
animals  and  that  he  bad  the  honesty  to  begin  upon  himself  the 
researches  which  he  wished  to  pursue  on  man;  finally,  although  he 
failed  from  a  practical  standpoint,  he  se1  forth  some  interesting 
considerations,  and  seemed  to  have  a  foresigh.1  of  exaltation  and 
attenuation  of  viruses. 

At  present  n<>  strong  viruses  are  inoculated  into  man,  bu1  they 
tire  inoculated  into  animals.  This  is  (lie  principle  of  the  method 
employed  against  symptomatic  anthrax,  murr  (foot-and-mouth 
disease),  and  peripneumonia.  In  order  to  render  the  inoculation 
inoffensive,  it  is  practised  in  those  regions  of  the  body  in  which  a 
thick  cellular  tissue  offers  a  certain  resistance  to  the  multiplication 
of  the  pathogenic  agents. 

Antivariolar  Vaccination.  The  inconveniences  of  the  preceding 
methods  are  no  longer  found  in  the  case  of  vaccinia. 

It  had  long  been  known  in  certain  regions  of  England,  and  notably 
in  the  county  of  Gloucester,  that  individuals  breeding  cows  often 
presented  in  their  fingers  small  pustules  contracted  on  contact  with 
animals  afflicted  by  cowpox,  and  that  this  eruption  conferred  upon 
them  immunity  from  variola.  In  1768  Sutton  and  Fewster  drew 
attention  to  these  facts.  It  was  then  that  Jenner  conceived  the  idea 
of  practising  in  a  systematic  manner  and  with  a  prophylactic  view 
the  inoculation  of  cowpox.  In  1798  he  published  the  result  of  his 
researches.  He  demonstrated  the  inoculability  of  coAvpox  from  cow 
to  man,  and  its  transmission  from  man  to  man.  and  showed  that 
immunization  was  surely  conferred  by  the  inoculation  of  the  vaccine. 

The  interesting  question  was  then  and  still  is  asked:  What  are 
the  analogies  existing  between  vaccinia  and  variola?  It  is  certain 
that  clinically  the  two  diseases  are  absolutely  distinct.  To  be  con- 
vinced of  this  it  suffices  to  examine  a  man  attacked  simultaneously 
by  both  of  these  diseases.  The  objective  characters  of  the  variola 
and  of  the  vaccinal  pustules  are  not  at  all  similar.  At  present, 
however,  when  we  are  well  acquainted  with  the  variability  of  viruses, 
we  may  ask  whether  the  differences  are  as  great  as  one  might  believe, 
whether  vaccinia  and  variola  do  not  have  a  single  origin,  and  wh ether 
the  virus  has  not  been  modified  through  repeated  passages  in  man 

54 


850  ISFECTIOUS  DISEASES. 

and  in  animals.  Dualists,  among  them  Chauveau,  remark  that  the 
objective  characters  are  different,  that  the  receptivity  of  animals 
is  not  similar,  and  particularly  that  the  variolar  virus  is  not  trans- 
formed into  vaccinia  through  passages  in  cows.  The  latter  argument 
is  not  perhaps  irrefutable,  for  it  may  be  answered  that  inoculations 
in  series  have  not  been  sufficiently  numerous.  On  the  other  hand, 
the  fact  itself  has  been  contradicted.  Voigt  (1881),  Fischer  (1885), 
Eternod  and  Haccius  (1892)  assert  that  by  practising  inoculations 
on  large  surfaces  they  have  transformed  variola  into  vaccinia,  and, 
transferring  their  experimental  results  to  the  domain  of  practice, 
they  have  prepared  a  vaccine  of  variolar  origin  which  has  given 
excellent  results. 

Although  the  question  presents  great  theoretical  interest,  it  seems 
to  be  of  little  consequence  from  a  practical  standpoint.  Vaccinia, 
which  seems  to  be  weakened  when  it  is  inoculated  from  man  into 
man,  according  to  the  Jennerian  method,  preserves  all  its  activity 
when  it  is  cultivated  in  cows.  A  second  problem,  however,  arises. 
Its  human  origin  being  denied,  it  remains  to  learn  whether  vaccinia 
is  originated  in  the  cow  or  in  the  horse.  Jenner  supposed  cowpox 
originated  from  horsepox,  and  described  the  disease  of  the  horse 
under  the  name  "  grease."  This  gave  rise  to  confusion.  The  word 
"grease"  was  translated  by  the  expression  "eaux  aux  jambes  " — 
an  expression  applied  to  osteitis  of  the  foot.  It  was  not  until  after 
the  contributions  of  Sarrans  and  Lafosse  that  it  was  understood 
that  Jenner 's  grease  is  the  disease  of  the  horse,  formerly  designated 
under  the  name  ' '  morve  volante ' '  (flying  glanders) .  Lafosse  showed 
that  the  virus  is  readily  inoculated  from  the  horse  to  the  cow,  and 
that  it  produces  in  the  latter  a  typical  vaccinia.  Chauveau  showed 
later  on  that  the  inoculation  of  horsepox  produces  in  children  an 
aborted  vaccinia  only ;  he  concluded  therefrom  that  vaccinia  acquired 
all  its  activity  in  the  cow,  and  that  it  represents  a  bovine  infection 
and  not  an  infection  of  the  horse.  It  is  to  be  noted,  on  the  other 
hand,  that  vaccinia  is  transmissible  to  a  great  number  of  animal 
species,  notably  to  dogs,  sheep,  goats,  and,  at  least  in  certain  cases, 
to  rabbits. 

At  present  it  may  be  stated  that  the  vaccinal  virus,  owing  to 
numerous  passages  which  it  has  undergone  in  cows,  has  become  a 
fixed  virus:  its  inoculation  is  almost  invariable.  In  individuals 
vaccinated  for  the  first  time,  the  eruption  begins  seventy-two  hours 
after  inoculation,  and  is  clearly  manifest  in  the  course  of  the  fourth 
day.     Even  with  this  fixed  virus,  however,  certain  variations  are 


HYGIENE  ANl>  I'lun'UYLAXis  OF  INFECTIOUS  DI8EASE8.    H'j) 

observed.   The  incubation  often  lasts  lour  or  five  cU  ptionally 

six  or  seven. 

The  inoculation  is  generally  practised  by  three  epidermal  punc- 
tures or,  still  bettor,  by  superficial  scarifications.  The  eruption  it 
localized  at  the  infected  points,  and  i1  i  altogether  exceptional  to 
sec  it  generalize.  In  the  latter  case  the  disea  e  assume  the  character 
of  a  quite  serious  infection,  accompanied  by  fever.  Kvei  ome  <■:>-(■- 
of  death  in  young  children  have  been  reported.  Tnis  eventuality, 
however,  is  so  extraordinary  thai  it  hardly  deserve*  to  I"-  taken  into 
account.  The  generalization  evidently  indicates  a  peculiar  suscep- 
tibility to  vaccinia,  and  probably  to  variola.  Barring  these  I 
examination  of  (lie  locnl  lesion  produced  by  inoculation  liki 
demonstrates  that  individuals,  according  to  previous  dl  i 
vaccinations,  according  to  their  innate  or  inherited  characters, 
according  to  a  number  of  intercurrent  circumstances,  present 
peculiar  resistance  or  susceptibilities.  The  regular  vaccinia  begins 
on  the  third  day  with  a  papule,  which  is  transformed  into  a  vesicle 
on  the  fifth,  and  reaches  maturity  on  the  seventh.  At  this  moment 
the  lesion  is  constituted  by  a  large  flat,  umbilicated  vesicle,  sur- 
rounded by  a  red  areola  and  containing  a  clear  and  thick  fluid. 
Toward  the  eleventh  day  the  crust  appears,  which  is  exfoliated  from 
the  twenty-first  to  the  twenty-eighth  day,  leaving  an  indelible 
cicatrix.  In  certain  instances  the  evolution  is  more  rapid,  the 
vesicle  remains  small,  and,  within  a  few  days,  its  evolution  is  termin- 
ated. This  vaccinoid,  which  has  improperly  been  called  pseudo- 
vaccinia,  simply  indicates  a  slight  resistance  of  the  organism,  and 
it  seems  to  me  to  prove  that  immunity  requires  to  be  reinforced  in 
such  cases. 

The  evolution  of  vaccinia  is  followed  by  a  modification  in  the 
body  fluids,  which  has  been  clearly  demonstrated  by  the  researches 
of  Sternberg,  Beclere,  Chambon,  and  Menard.  This  is  a  particular 
instance  in  perfect  harmony  with  our  present  knowledge  of  the  mech- 
anism of  artificial  immunity.  As  always,  however,  the  modifications 
thus  produced  in  the  organism  are  not  permanent.  At  the  end  of 
a  certain  length  of  time  immunity  disappears.  It  is  generally 
estimated  that  adults  should  be  vaccinated  once  every  ten  years: 
children  whose  nutrition  is  more  active  more  rapidly  lose  their 
vaccinal  immunity,  and  must  be  revaccinated  once  every  seven  or 
eight  years.  These  data  are  perfectly  acceptable.  It  should  be 
remembered,  however  that  one  vaccination  does  not  suffice  to 
extinguish  variola  in  a  definitive  maimer.     The  countries  where 


852  INFECTIOUS  DISEASES. 

vaccination  is  compulsory  are  not  free  from  the  disease.  For  ex- 
ample, in  Sweden,  where  the  mortality  was  165  per  100,000  inhab- 
itants before  the  introduction  of  vaccine,  fell,  since  the  discovery 
of  vaccination,  to  55,  and  since  vaccination  was  made  compulsory, 
to  IS.  In  Germany,  where  law  prescribes  vaccination  and  re- 
vaccination,  the  mortality  is  only  2.2  per  100,000  among  the  civilian 
population,  while  in  the  army,  in  which  the  rules  are  better  observed, 
variola  may  be  said  to  be  unknown.  It  would,  therefore,  be  easy, 
through  an  international  agreement,  to  cause  the  disappearance  of 
variola.  So  far  as  France  is  concerned,  we  know  at  present  that 
variola,  although  sufficient^  rare,  is  still  observed,  particularly  in 
certain  cities,  such  as  Marseilles.  In  1900  we  had  in  Paris  a  quite 
severe  epidemic,  which  continued  and  even  increased  the  following 
year.  At  the  time  an  epidemic  is  prevailing  the  resistance  conferred 
by  previous  vaccinations  should  not  be  counted  upon;  variola  itself 
does  not  create  absolute  immunity.  A  certain  number  of  recur- 
rences have  been  reported,  and  Heim,  by  revaccinating  individuals 
who  had  once  had  variola,  obtained  32  per  cent,  of  complete  suc- 
cesses, 25  per  cent,  of  incomplete  successes,  and  42  per  cent,  failures. 
According  to  the  wise  advice  of  Dr.  Hervieux,  in  ordinary  times 
individuals  should  be  vaccinated  at  the  age  of  ten,  and  then  again 
at  the  age  of  twenty.  At  the  time  of  an  epidemic,  however,  every- 
body should  be  vaccinated.  It  is  also  to  be  remembered  that  the 
aged  are  not  refractory,  as  is  generally  supposed.  Facts  recorded 
by  Beclere  and  Brot1  are  absolutely  conclusive.  Everybody  should, 
therefore,  be  revaccinated,  since  the  duration  of  immunity  is  not 
fixed,  and  it  is  not  known  at  the  end  of  how  much  time  it  disappears. 
Thus,  in  1897,  we  noticed  that  vaccinia  succeeded  for  the  second 
time  in  six  children,  the  oldest  of  whom  was  five  years  and  the 
youngest  sixteen  months  old.2  In  all  of  these  indubitable  cicatrices 
of  a  previous  vaccination  were  present.  These  subjects  were,  there- 
fore, in  a  state  of  receptivity.  Several  personal  observations  of 
mine  could  be  cited  in  support  of  this  conclusion.  The  most  inter- 
esting of  these  observations  is  that  concerning  a  pregnant  woman, 
already  referred  to  (p.  590),  who  had  been  successfully  vaccinated 
at  the  seventh  month  of  her  pregnancy,  and  two  months  later  con- 
tracted a  benign  variola  which  she  communicated  to  her  child, 
The  latter,  owing  to  the  influence  of  the  maternal  vaccination, 
resisted  the  infection  fairly  well. 

1  Brot.     De  Pimmunit£  vaccinale.     These  de  Paris,  1897. 

2  Roger.     Sur  la  duree  de  1'immunit^  vaccinale.     Soci£t6  de  Biologie,  July  2,  1897. 


HYGIENE  AND  PBOPHYLAXIS  OF  INFECTIOUS  DISEASES. 

The  conclusion  is  unavoidable:  a1  timet  of  epidemic 
must  be  vaccinated.    Ai   ordinary  time    revaccination  ihould  be 
practised  once  every  ten  years.     [1  I    ai  o  to  be  remembered 
if  a  previous  vaccination  does  no1  Becure  ab  olute  immunity 
variola,  it  decreases  the  gravity  of  the  infection  and  thai  the  i 
tality  is  very  low  in  revaccinated  individuals.    Of  mdividuak  who 
have  been  vaccinated  three  times  we  have  losl  only  three  in  our 

wards. 

The  statistics  of  the  Westham-Union  Bospital,  bearing  upon  WOO 
eases  observed  from  IS77  to  L882,  furnished  the  following  results, 

which  need  no  comment  :' 

Ca  •       Mori 

•      ,    i        •   i  I  IT  50.4 

Non-vaccinated  vanola 

Not  well  vaccinated 

Vaccinated  \  ariola  casea 

Vaccinated  and  re>  accinated  ca  e         ... 

Dr.  Delom2  who,  from  this  point  of  view,  tabulated  L023  obser- 
vations taken  in  our  hospital  in  1900  and  at  the  beginning  of  L901, 

obtained  the  following  results:  ^    ^^  ^  ^ 

.     l                                                                           .      77  52 

Non-vaccinated . 

Vaccinated  once  withoul  success 

Vaccinated  once  with  success ' ( " ' 

Vaccinated   with  success  and  revaccinated   without 

.    inn  L3  13.0 

success 

Vaccinated  and  revaccinated  with  success       ...     89  is  <_ 

Vaccinated  while  in  incubation  of  variola  .      ...     39 

If  the  age  of  the  individual  is  considered,  the  following  interesting 
results  are  obtained,  which  we  sum  up  as  follows: 


78 

7'.»J 
21 


19 

S6 


27  1 

10.7 
«t 


1 

Vaccinated  once. 

Revaccinated. 

.... 

Vaccinated 

Age  of  patient. 

Non-vaccin- 
ated. 

Successfully.    ^lly?8" 

Successfully.    Uu^veS9' 

in  incuba- 
tion. 

Cases. 
Deaths. 

- 

3 

- 

- 
s> 

* 

Cases. 

1  >l'll  t  1  IS. 

- 
- 

- 

-s. 

9 
CO 

s 

Deaths. 
Per  ct. 
Cases, 
Deal  b 
I'er  ot. 

-              ~               ._ 
5               - 

_              -             - 

0-  5  years 

39 

28 

71.7 

4 

1 

25.0 

5 

3 

60.0 

0 

0     0         0       0       0 

13       6    46.1 

6-10     " 

1 

0 

0 

10 

2 

20.0 

3 

1 

33.3 

1 

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i  Report  on  1000  cases  of  smallpox  in  Westham-TJnion  Hospital.  Lancet.  July  22,  L882 
»  Delom.     De  Finfluence  de  la  vaccine  sur  la  variole.     Thfee  de  Paris.  1901. 


854  INFECTIOUS  DISEASES. 

Although  vaccination  is  not  compulsory  in  France,  most  of  the 
inhabitants  of  that  country  have  undergone  at  least  one  inoculation. 
A  certificate  of  vaccination  is  required  of  children  to  be  admitted  to 
schools.  All  recruited  men  to  the  regiments  are  revaccinated.  The 
influence  of  the  vaccinations  practised  in  the  army  explains  why  men 
from  twenty  to  thirty  years  of  age  are  far  less  frequently  attacked 
by  variola  than  women.  In  large  administrations  revaccinations  are 
often  practised.  According  to  information,  however,  which  the 
author  obtained  during  the  last  epidemic,  private  establishments  are 
often  better  organized  from  this  standpoint  than  public  establish- 
ments. Furthermore,  a  measure  has  been  adopted  which  seems  to 
have  very  gratifying  results :  When  a  case  of  variola  is  reported  in 
a  house  a  vaccine-bearing  heifer  is  sent  to  the  house  and  employed 
for  vaccinating  all  the  residents  free  of  charge.  Many  persons  who 
would  not  otherwise  take  the  trouble  thus  consent  to  be  inoculated 
at  home.  Owing  to  these  various  measures  variola  has  been  con- 
siderably decreased;  the  epidemic,  however,  which  recently  prevailed 
shows  that  it  may  easily  again  be  increased.  It  would,  therefore,  be 
advisable  to  do  in  France  what  is  being  carried  out  in  a  great  number 
of  countries,  notably  in  Germany.  Two  inoculations  suffice,  on  con- 
dition, of  course,  that  all  the  inhabitants  be  submitted  to  it.  One 
to  be  practised  during  first  childhood  (under  two  years  of  age),  the 
other  at  the  age  of  twenty  years.  The  efficacy  of  the  method  is 
demonstrated  by  German  statistics.  The  results  are  so  clear  that 
some  authors  have  declared  variola  to  be  a  disease  of  historical 
interest,  since  it  is  no  longer  observed  in  civilized  countries. 

Immunization  by  Attenuated  Viruses.  Instead  of  introducing  into 
the  organism  a  mild  natural  virus  capable  of  conferring  immunity, 
modified  infectious  agents  may  be  employed,  namely,  such  agents 
as  have  been  deprived  of  part  of  their  virulence,  in  other  words, 
attenuated  viruses.  Such  is  the  principle  of  a  new  method  called 
Pasteurian  vaccinations. 

Attenuation  may  be  obtained  by  a  great  number  of  procedures. 
Most  of  these  consist  in  cultivating  the  virulent  agent  under  dys- 
genesic  conditions  or  disturbing  its  vitality  by  physical  or  chemical 
means.  The  age  of  cultures,  heating,  exposure  to  sun  rays,  develop- 
ment at  high  temperatures,  the  addition  of  antiseptic  substances  to 
the  culture  medium,  the  influence  of  compressed  oxygen — such  are 
the  most  usual  procedures.  Let  us  add  to  these  inoculation  into 
certain  animals :  the  virus  becomes  exalted  for  the  species  upon  which 


HYGIENE  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES, 

the  experiment  is  performed,  while  it  become  attenuated  a 
another  species,  a  result  which  may  I"'  employed  a   an  argument  of 
the  original  unity  of  variola  and  of  vaccinia.    Bowever  thu  may  be, 
Pasteurian  vaccinations  are  exclusively  employed  in  veterinary  medi- 
cine and  give  remarkable  results  againsl  anthraj      B 
various  systems  of  vaccination  againi  I  anthrax  animale  sensitr 
this  disease  have  successfully  been  rendered  refractory.    Everyone 
remember*  (lie  famous  experimenl  of  Pouilly-le  Fort,  where  Pasteur 
conclusively  demonstrated  the  value  of  his  method.    At  pri 
there  is  not  the  slightest  shadow  of  doubl  as  to  the  efficacy  of  the 
method.    From  L882  to  L894,  1,788,677  sheep  have  been  vaccinated 
in  France,  and  their  mortality  has  been  0.9 1  per  cent .,  while  formerly 
it  readied  10  per  cent.    As  regards  cattle,  200,962  have  been  inocu- 
lated, and  the  mortality  has  fallen  from  5  per  cent .  to  0.3 1  per  cent .' 
Numerous  laboratories  of  vaccination  have  been  organized  in  foreign 
countries  (Vienna,  .Madrid,  Turin,  Buenos  Ayres,  Odessa,  etc.  ,  and 
their  results  have  confirmed  the  efficacy  of  the  method. 

Vaccination  against  Hydrophobia.  These  results  suggest  the  Ques- 
tion whether  vaccines  could  not  act  even  after  the  introduction  of 
an  active  virus.  It  was  likewise  Pasteur  who  took  up  and  solved 
this  problem.  Into  individuals  bitten  by  a  rabid  animal  are  prac- 
tised injections  with  the  diseased  spinal  cord  attenuated  by  desicca- 
tion. A  refractory  state  is  thus  created  which  develops  more 
speedily  than  the  disease.  Immunity  is  immediately  manifest  to 
prevent  the  propagation  of  the  active  virus  and  enable  the  organism 
to  destroy  it. 

It  was  by  studying  the  action  of  the  hydrophobic  virus  and  by 
seeking  to  vaccinate  against  it  that  Pasteur  was  led  to  this  new 
result.  It  should  not  be  forgotten,  however,  that  the  first  attempt 
of  vaccination  against  hydrophobia  is  due  to  Gautier.  In  a  note 
presented  to  the  Institute.  January  25,  1881,  this  scientist  announced 
that  the  injection  of  hydrophobic  saliva  into  the  veins  of  sheep  does 
not  produce  hydrophobia,  but  confers  immunity.  This  result,  which 
was  confirmed  August  1.  1SS1.  in  a  contribution  in  which  the  author 
announced  that  he  had  vaccinated  nine  sheep  and  one  goat,  wj  - 
considerable  interest.  Unfortunately,  the  method  was  unfit  for  prac- 
tical purposes,  because  the  introduction  of  saliva  is  an  unreliable  and 
dangerous  method.     Intravenous  injection,  which  succeeds  so  well 

1  Chamberlaiul.  Resultats  pratiques  des  vaccinations  coutre  le  charbon.  Annates  de 
I'Institut  Pasteur.  1894. 


856  ixfecti o  us  I) is /■:. i  .s  /; s. 

with  ruminants,  in  most  cases  causes  death  "when  it  is  applied  to 
other  animals,  and  particularly  to  the  dog. 

In  1SS1  Pasteur,  Chain) >erland  and  Roux,  and  Thuillier  published 
a  method  which  did  away  with  all  the  uncertainty  of  inoculation  of 
saliva:  This  was  the  employment  of  the  hydrophobic  spinal  cord, 
an  emulsion  of  which  was  injected  beneath  the  dura  mater.  In  1882 
Pasteur  and  his  collaborators  announced  that  of  three  dogs  inocu- 
lated two  perished  and  one  survived  after  having  been  sick  this 
animal  had  become  refractory ;  it  was  subsequently  twice  inoculated 
by  trepanation,  but  did  not  become  hydrophobic.  From  that  time 
on  Pastern'  saw  several  dogs  inoculated  with  virulent  matter  resist 
the  experiment  and  become  refractory.  He  even  noticed  that  large 
doses  of  hydrophobic  virus,  when  injected  beneath  the  skin,  produce 
hydrophobia  less  frequently  and  immunity  oftener  than  medium 
doses.  This  result,  highly  interesting  from  the  standpoint  of  patho- 
logical physiology,  was  confirmed  by  various  experimenters,  notably 
by  Bardach.  Under  these  conditions,  however,  vaccination  appears 
as  an  exceptional  fact;  it  was,  therefore,  necessary  to  prepare  a  virus 
incapable  of  killing  the  dog,  but  sufficient  to  increase  its  resistance 
and  render  it  refractory  to  more  and  more  energetic  agents.  This 
attenuation  of  virulence  Pasteur  obtained  by  transferring  hydro- 
phobia from  the  dog  to  the  monkey.  As  passages  are  practised  upon 
the  latter  animal  the  activity  of  the  virus  weakens,  a  fact  proved 
by  the  progressive  lengthening  of  the  period  of  incubation.  If 
the  virus  is  then  transferred  to  the  rabbit,  it  becomes  exalted;  the 
period  of  incubation  gradually  decreases  until  the  minimum  point  is 
reached. 

This  minimum  delay  of  incubation,  obtained  at  about  the  hun- 
dredth passage,  is  invariable,  and  amounts  to  six  or  seven  days.  The 
virus  is  then  said  to  be  "  fixed." 

Thus,  starting  from  the  monkey  and  passing  through  the  rabbit, 
one  may  prepare  a  series  of  viruses  with  progressively  decreasing 
activity.  If  we  inoculate  beneath  the  skin  of  a  dog  the  more  and 
more  virulent  spinal  cord  of  a  rabbit,  beginning  with  the  least 
energetic,  we  produce  no  accident,  but  confer  on  the  dog  immunity 
against  the  most  virulent  virus  introduced  by  trepanation.  This 
result,  based  upon  twenty-three  experiments,  was  announced  to  the 
Institute  on  May  19,  1884,  and  confirmed  by  the  researches  pursued 
upon  forty-two  inoculated  and  forty-two  controlled  animals,  before 
a  commission  composed  of  Beclard,  Bouley,  Bert,  Vulpian,  and  Vil- 


HYGIENE  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES.    857 

Iciniii.    When  bitten  by  rabid  dog  ,  no1  one  of  the  vaccinated  animals 
succumbed,  while  mosl  of  the  controls  perished. 

The  discovery  was,  therefore  achieved,  bu1  the  method  wat  not 
practical.  It  was  necessary  to  suppress  the  pai  age  through  the 
monkey  and  attenuate  the  virus  withoul  employing  this  animal. 
This  new  problem  was  likewise  solved  by  Pa  teurand  hit  collabora- 
tors. They  took  rabbits  which  had  died  from  the  "  fixed  "  virus,and 
they  found  thai  their  spinal  cords  lost  much  of  their  virulence  under 
the  influence  of  desiccation.  In  order  to  obtain  thif  result,  these 
spinal  cords  are  detached  with  thegreate  I  a  eptic  precautions;  they 
are  suspended  in  a  vial  closed  with  cotton  and  .'if  the  bottom  of 
which  there  are  fragments  of  potassium.  From  the  thirteenth  to  the 
fourteenth  day  on,  the  cord  is  found  to  have  losl  ite  virulence; 
the  shorter  the  period  of  desiccation  the  greater  Ls  the  activity  of  the 
conl.  In  1885  Pasteur  uniioiiiiceil  that,  l>y  means  of  spinal  cords 
thus  prepared,  he  had  rendered  fifty  dogs  refractory  to  inoculations 
practised  into  the  skin  and  even  beneath  the  dura  mater. 

In  view  of  the  results  given  by  this  memorable  experiment,  an 
attempt  might  he  made  to  apply  to  man  the  new  method.  The 
occasion  soon  presented  itself.  As  is  well  remembered,  the  firsl 
attempt  was  made  upon  young  Joseph  Meister,  bitten  July  4,  1885. 
After  consulting  Professors  Vulpian  and  Grancher,  Pasteur  practised 
his  mode  of  treatment  upon  this  child,  who  seemed  to  be  condemned 
to  certain  death  by  the  number  and  depth  of  the  bites.  The  result 
exceeded  all  expectation.  The  patient  recovered,  and  sixteen  ; 
after  the  inoculation,  he  was  in  perfect  health. 

After  this  first  case,  which  was  reported  in  October.  1885,  very 
large  numbers  of  individuals  have  come  to  the  laboratories  of  Pasteur 
from  all  parts  of  the  world.  More  than  ten  thousand  have  been 
treated  in  Paris;  at  least  as  many  have  been  similarly  Treated  in  the 
Pasteur  Institutes  of  foreign  countries.  Pasteur  first  employed  a 
simple  method,  which  consisted  in  injecting  beneath  the  skin  the 
spinal  marrow  of  the  fourteenth  day,  then  successively  those  of  the 
thirteenth,  twelfth,  until  the  fifth  day.  Each  specimen  of  marrow 
was  injected  once;  the  treatment,  therefore,  lasted  ten  days.  This 
method  was  not  sufficient  for  grave  cases:  hence.  Pasteur  abandoned 
it  and  adopted  the  so-called  intensive  method,  which  consists  in 
repeating  the  inoculations,  in  making  the  vaccinations  at  shorter 
intervals,  and  in  administering  more  virulent  marrow.  The  treat- 
ment is  modified  according  to  the  gravity  and  especially  the  seat  of 


858  IXFECTIO  US  DISEASES. 

the  bites.  The  method  is  carried  out  as  follows:  A  fragment  of 
spinal  marrow  about  3  mm.  long  is  taken  and  triturated  in  1  c.cm. 
of  bouillon  and  injected  beneath  the  skin  in  the  hypochondriac 
region.  The  injection  is  somewhat  painful,  but  gives  rise  to  no  dis- 
turbance except  in  the  last  two  days,  when  the  puncture  becomes  the 
seat  of  a  small  erythematous  and  itching  patch.  First,  a  specimen 
of  the  marrow  of  fourteen  or  thirteen  days  is  employed,  then  pro- 
gressively the  marrows  of  twelve  and  eleven  until  that  of  the  third 
day  is  reached,  the  virulence  of  the  latter  being  about  the  same  as 
that  of  the  fresh  marrow.  The  quantity  injected  may  reach  3  c.cm. 
in  the  case  of  marrows  of  little  activity — those  of  the  fourteenth  to 
seventh  day — no  more  than  2  c.cm.  of  the  marrow  of  less  than  seven 
days  are  given.  In  grave  cases  intervention  must  be  prompt,  there- 
fore four  injections  a  day  are  given.  The  first  day  the  marrows  of 
the  fourteenth  and  thirteenth  days  are  employed  by  two  punctures, 
one  in  each  hypochondriac  region;  in  the  evening  of  the  same  day 
the  marrows  of  the  twelfth  and  eleventh  days  are  injected.  The 
following  day  the  marrows  from  the  tenth  to  the  seventh  day  are 
used.  On  the  third  day  of  the  treatment  two  injections  are  given 
with  the  marrow  of  the  sixth  day.  After  that,  one  injection  is  given 
daily  with  the  more  virulent  marrows.  When  the  marrow  of  the 
third  day  is  reached  a  new  series  is  begun,  starting  with  the  marrow 
of  the  fifth  clay;  then  recourse  is  had  to  a  third  and  even  a  fourth 
series.  At  times,  at  the  end  of  the  treatment  the  patient  complains 
of  pain  at  the  point  of  the  cicatrices ;  in  such  cases  a  new  vaccination 
is  undertaken  according  to  the  intensive  method,  and  the  symptoms 
often  disappear.  It  is  thus  conceivable  that  the  vaccination  must 
not  be  applied  in  the  same  manner  in  all  patients ;  we  cannot,  however, 
dwell  upon  the  details  of  the  treatment,  which  varies  with  each  case, 
and  the  duration  of  which  is  limited  between  fifteen  and  twenty-two 
days. 

Pasteur's  method  is  at  present  employed  in  a  great  number  of 
countries;  it  has  at  times  undergone  more  or  less  important  modifi- 
cations. Thus,  in  countries  where  rabbits  are  smaller  than  ours  the 
spinal  marrows  dry  rapidly  and  lose  their  virulence  more  speedily. 
It  is,  therefore,  possible  to  begin  the  injections  with  marrows  of  the 
tenth  or  eighth  days,  as  is  done  by  Babes  in  Bucharest,  and  Bujwid 
in  Warsaw.  The  latter  experimenter  gives  the  series  of  marrows 
from  the  twelfth  to  the  third  days  in  four  days,  and  repeats  the  same 
series  three  times.    In  desperate  cases  Bardach  and  Gamaleia  have 


HYUTKNK  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES.    Hr,<) 

employed  the  entire  series  of  viruses  each  day  for  three  da; 
cession,  reaching  the  specimen  of  one  day.    I1   i     nun''' 
mention  all  the  modifications  of  the  treatment.    Reference  musl  be 
made  to  the  attempt  of  Ferran,  who  did  qo1  he  itate  to  injeci  non- 
attenuated  viruses.    Although  his  method  seems  id  have  given  j 
results,  it  has  produced  disturbances  in  Milan  at  the  hands  of  Bareggi. 

It  has  likewise  been  possible,  at  leasl  In  the  case  of  animal 
confer  immunity  against  hydrophobia  by  other  procedures.  I>r. 
Galtier's  experiments  have  already  been  alluded  to.  More  recently 
Drs.  Nocard  and  Roux  have  taken  up  the  method  of  intravenous 
injections  by  substituting  for  saliva  ;i  more  certain  virus  furnished 
by  an  emulsion  of  spinal  marrow.  They  have  thus  succeeded  in  vac- 
cinating sheep,  and  even  saving  several  into  the  eyes  of  which, 
twenty-four  hours  previously,  they  had  inoculated  the  virus  of  hydro- 
phobia. Intravenous  injection  may  also  confer  immunity  upon  the 
dog,  provided  a  weak  virus  be  first  employed,  and  then  gradually 
specimens  of  progressively  growing  activity  (Protopopoff).  More- 
over, vaccinations  have  also  been  practised  by  means  of  diluted 
viruses  (Bardach),  as  well  as  with  viruses  attenuated  by  heal    I ' 

The  brief  history  of  facts  above  given  demonstrates  that  the  virus 
of  hydrophobia,  when  rendered  inoffensive  by  one  of  the  foregoing 
procedures,  may  confer  immunity.  The  mechanism  by  which  this 
effect  is  obtained  has  been  a  question.  In  view  of  the  results  ol  iservei  I 
in  other  infectious  diseases,  an  effort  has  been  made  to  learn  whether 
antirabic  vaccination  does  not  depend  upon  soluble  substances  elab- 
orated by  the  agent  of  hydrophobia.  Prof.  Bouchard  attempted  to 
vaccinate  by  means  of  marrow  triturated  in  water  and  filtered 
through  porcelain.  The  fluid  thus  obtained  did  not  confer  immunity 
against  inoculation  later  practised  beneath  the  dura  mater.  This 
negative  result  was  confirmed  by  De  Blasi  and  Travali.  These 
authors  succeeded,  however,  in  rendering  animals  refractory  to  intra- 
venous inoculations  by  the  same  procedure.  Babes  and  Lepp  have 
likewise  conferred  immunity  by  injecting  cerebral  substance  sterilized 
by  heating  at  176°  F.  (80°  C). 

Pasteur  thought  that  his  procedure  did  not  attenuate  the  virus  but 
decreased  its  quantity.  A  rabbit  into  which  this  so-called  attenu- 
ated virus  is  injected  succumbs  in  thirty  days,  and  its  medulla  as 
well  as  the  fixed  virus,  when  inoculated  mto  a  second  rabbit,  kills 
the  latter  in  seven  days.  Desiccation  is  supposed  to  destroy  the 
virus  more  rapidly  than  the  vaccine,  so  that  the  marrows  rapidly  lose 


860  INFECTIOUS  DISEASES. 

their  noxious  properties,  while  they  preserve  their  vaccinating  prop- 
erties for  a  longer  time. 

The  attenuation  of  marrow  attributed  by  Protopopoff  and  Blasi 
and  Russo-Travali  to  the  action  of  heat  seems  to  depend  upon  a 
phenomenon  of  oxidation  brought  about  by  heat.  Thus,  Zagari  has 
found  that  marrows  placed  in  dry  air  remain  virulent  for  ten  days 
at  a  temperature  of  68°  F.  (20°  C),  and  for  only  sixty-six  hours  at 
95°  F.  (35°  C).  The  virulence  is  more  rapidly  lost  in  hydrogen;  it 
is  preserved  longer  in  vacuo,  and  especially  in  carbonic  acid.  If  it 
disappears  under  these  conditions,  it  is  due  to  the  fact  that  the 
marrow,  at  the  time  it  is  taken  from  the  body,  retains  a  certain 
amount  of  oxygen  which  serves  the  ulterior  phenomena  of  oxidation. 
The  immunity  conferred  by  the  Pasteurian  method  seems  to  be  fairly 
durable.  It  persists  for  two  years  in  dogs.  It  may  be  transmitted 
even  by  heredity :  at  least  this  is  what  seems  to  be  proved  by  a  very 
interesting  fact  published  by  Hogyes:  of  four  young  born  from  a 
refractory  couple  and  inoculated  in  the  eye  when  three  months  old, 
one  died;  two  succumbed  after  a  very  long  incubation;  the  fourth 
survived  and  resisted  two  additional  inoculations. 

Such  are  the  facts  that  may  be  recorded  in  favor  of  Pasteur's 
method.  They  demonstrate  the  possibility  of  attenuating  or  rather 
modifying  the  virus  of  hydrophobia  and  that  this  modified  virus  ren- 
ders animals  refractory  to  hydrophobia  and  enables  bitten  individ- 
uals to  resist  the  infection. 

Immunization  against  Cholera,  Bubonic  Plague,  and  Typhoid  Fever. 
Haffkin  indicated  two  procedures  for  vaccinating  against  cholera. 
The  first  consists  in  injecting  an  attenuated  virus,  and  eight  days 
later  a  strong  virus.  The  second  procedure  is  based  upon  the  employ- 
ment of  cultures  sterilized  by  a  0.5  per  cent,  solution  of  carbolic  acid. 
Since  1893  the  anticholeric  vaccine  has  been  inoculated  in  India  into 
more  than  100,000  individuals.  The  mortality  is  said  to  have  been 
diminished  by  about  15  to  20  per  cent.  However,  strange  to  relate, 
while  cholera  is  less  frequent  among  vaccinated  individuals,  it  seems 
to  be  just  as  grave  when  it  attacks  them. 

In  order  to  prevent  bubonic  plague  Haffkin  employed  cultures  of 
the  bubonic  bacillus  heated  to  161.5°  F.  (72°  C).  The  immunity 
thus  conferred  lasts  more  than  six  months.  Statistics  seem  to  show 
that  the  prophylactic  results  are  quite  clear.  Morbidity  is  decreased, 
and  the  mortality,  which  is  62  per  cent,  in  non-vaccinated  subjects, 
falls  to  27  per  cent. 


HYGIENE  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES.    H(;i 

Finally,  lei  us  mention  the  attempts  of  Wright,  who  vaccini 
against  typhoid  fever  by  means  of  culture  sterilized  by  heat.    I 
inoculations  have  been  practised  in  Mi''  army  of  India,  and  have 
reduced  the  number  of  cases. 

Dangers  of  Vaccinations.      A  grave  objection   may   bo  made  againsi 

all  these  methods.    An  infection,  whatever  ii  may  be,  and  how< 
benign  that  it  may  besupposedto  be,  gives  rise  to  a  seri  turb- 

ances  and  lesions.    It  produces  in  the  organism  nutritional  modifi- 
cations and  changes  in  the  constitution  of  the  fluids,  which  account 
for  the  immunity  acquired.    The  morbid  work  may  !"■  so  slighl  :i 
to  be  unnoticeable.    We  cannot,  however  deny  the  reality,  and 
sequently  we  must,  in  a  certain  measure,  fear  these  new  methods. 

Breeders  assert  thai  sheep  h unized  againsi  anthrax  do  not 

develop  as  well  as  others.  Hence,  vaccination  is  practised 
larly  in  Beaucc.  The  losses  caused  by  ;i  lew  cases  of  anthrax  are 
less  considerable  than  depreciation  resulting  from  immunization. 
Upon  the  author's  advice,  Dr.  Kaplan1  studied  this  question.  Be 
examined  two  lots  of  sheep,  one  vaccinated,  the  other  not  vaccinated. 
By  watching  the  animals  and  weighing  them  regularly,  he  found  no 
notable  differences.  It  has  also  been  questioned  whether  vaccina- 
tions could  not  induce  a  fatal  infection  in  a  predisposed  individual 
who  is  already  sick  and  suffering.  What  we  have  learned  from 
experimentation  on  microbic  associations  gives  a  certain  importance 
to  this  criticism.  This  objection  has  been  raised  particularly  with 
regard  to  antirabic  treatment.  Leaving  aside  contestable  report s,  il 
must  be  remembered  that  eminent  bacteriologists,  like  Babies,  have 
cited  cases  in  which  vaccinal  hydrophobia  has  given  rise  to  disorders. 
These  cases  are  undoubtedly  exceptional;  they  do  not  impair  the 
value  of  the  method,  and  must  not  prevent  its  employment  against 
bites.  They  must  only  render  us  more  circumspect  when  the  ques- 
tion is  one  of  prophylaxis. 

Serum  Prophylaxis.  In  the  presence  of  the  inconveniences  result- 
ing from  the  introduction  into  the  organism  of  even  attenuated  living 
viruses  or  of  toxins,  attempts  have  been  made  to  secure  prophylaxis 
by  means  of  serums.  Preventive  inoculations  have  been  practised 
against  streptococcic  infections,  notably  puerperal  fever;  against 
bubonic  plague,  tetanus,  and  diphtheria.  Heubner  established  that 
injections  of  antidiphtheritic  serum  repeated  every  three  weeks  com- 

1   Kaplan.     Contribution  a.  l'etude  du  charbon.     Son  etat   actuel  en   Beauce.     These 
de  Paris,  1900. 


862  IXFECTIO  US  DISEA  SES. 

pletely  suppressed  the  contagion  in  the  hospitals.  For  his  part,  the 
author  believes  that  it  is  better  to  struggle  against  contagion  by- 
isolating  suspicious  cases.  The  author  never  resorts  to  preventive 
injections,  and  for  the  last  six  years  has  never  observed  a  single  inter- 
nal case.  He  believes,  however,  that  this  method  must  be  employed 
when  several  cases  occur  in  an  establishment  or  a  family.  In  other 
words,  preventive  serumtherapy  must  be  a  method  of  exception 
which  may  render  immense  service  in  certain  instances,  but  which 
must  not  be  laid  down  as  a  general  rule.  There  will  always  be  time 
enough  for  practising  injections  of  serum  when  the  infection  is  con- 
tracted. In  order  that  intervention  may  be  timely,  it  is  necessary 
to  watch  with  particular  care  individuals  who  have  been  in  contact 
with  diphtheria  cases.  This  reservation  is  confirmed  by  the  fact  that 
physicians  who  treat  diphtheria  cases  are  not  in  the  habit  of  prac- 
tising preventive  inoculations  upon  themselves  or  their  families.  The 
same  rules  are  applicable  to  other  serums.  If  an  epidemic  of  puer- 
peral fever  should  reign  in  a  ward,  it  would  be  advisable  to  practise 
prophylactic  injections  of  serum,  but  we  do  not  advise  to  thus  inject 
every  puerperal  woman.  Likewise,  antitetanic  serum  should  not  be 
employed  every  time  an  individual  happens  to  have  an  abrasion;  but 
it  will  be  useful  in  certain  regions  where  tetanus  is  endemic.  Lastly, 
the  antibubonic  serum,  although  less  efficacious  than  Haffkin's  vac- 
cine, has  the  advantage  of  being  less  dangerous.  It  may,  therefore, 
be  employed  at  the  time  of  an  epidemic. 

Thanks  to  the  multiple  procedures  which  we  possess  at  present,  it 
is  possible  to  confer  immunity  against  a  great  number  of  infections. 
A  more  and  more  accurate  knowledge  of  pathogenic  agents,  of  their 
distribution  in  nature,  their  mode  of  penetration  into  the  organism 
has  led  to  various  hygienic  measures  which  have  lowered  both  mor- 
bidity and  mortality.  The  isolation  of  contagious  cases,  sterilization 
of  contaminated  objects,  the  destruction  of  germ-bearing  organic  par- 
ticles often  suffice  to  arrest  the  spread  of  disease.  These  divers 
methods  are  no  more  than  a  systematization  of  ancient  ideas.  An- 
tiquity had  a  certain  foresight  of  the  results  obtainable  by  prophy- 
laxis, as  is  indicated  by  the  hygienic  laws  of  Moses  and,  in  the  middle 
ages,  the  creation  of  lazarettos  and  quarantines.  What  belongs  to 
the  modern  epoch  is  the  formulation  of  precise  rules  based  upon 
experimental  facts — substitution  of  scientific  data  for  intuition. 

Alongside  of  other  hygienic  measures  there  arises  a  new  method  of 
prophylaxis,  viz.,  vaccination,  likewise  an  ancient  method  originated 


HYGIENE  AND  PROPHYLAXIS  OF  INFECTIOUS  DISEASES. 

in  China.  Et  was  not  until  about  the  middle  of  the  eighteenth  century 
fchat  variolization  was  introduced  into  Europe.  I)  wbm  no1  long 
employed.  A  sure  and  inoffensive  method  for  this  uncertain  and 
dangerous  procedure  was  substituted  by  the  geniue  of  Jenner.  A 
century  later  another  genius,  Pasteur,  demonstrated  thai  an  artifi- 
cially modified  vims  could  be  placed  by  tie-  ride  <>('  ■■>  naturally 
inoffensive  virus.  A  new  prophylactic  method  thue  took  it-  | 
tion  among  the  means  which  enabled  mankind  to  Bghl  infections. 
Finally,  the  third  method  is  thai  which  was  developed  aboul  ten 
years  ago  as  a  resull  of  Uehring's  and   EGtasato'fi  laboi 

Prophylaxis  by  hygiene — i.  c,  by  isolation  and  disinfection 
prophylaxis  by  Jennerian  vaccination,  by  Pasteurian  vaccination, 
by  serumtherapy — these  are  the  great  methods  which  science  al  the 
beginning  of  the  twentieth  century  places  al  the  disposal  of  mankind 
for  combating  epidemics,  arresting  their  march,  and  lowering  their 
mortality. 


I  N  DEX. 


by 


,  220 

scrim 


injection  . 
characters   of, 


ABSCESS  of 
produced 
739 

Actinomyces,     biologic 

31  l 
cultivat ion  of,  -<\ 5 

Actinomycosis,  31  I 

etiology  of,  317 
evolution  of,  317 
inoculations  of,  316 
Adenopat  hies  in  smallpox,  386 
s\  philitic  and  tubercular,  386 
tracheobronchial,    KIT 
Age,  influence  of,  upon  prognosis,  632 
Albuminuria  caused  by  scrum  injections, 

742 
Alimentary   canal.     See   also    Digestive 
apparatus, 
antisepsis  of,  6<iS,  672 
combined  infect  ions  in,   1  IS 

gangrene  of,  241 

infection  by,  105 
putrefactions  in,   III 

suppurations  of,  21  I 

Alimentation,  841 
Aliments.     See  also  Fasting. 

role  of,  in    the  transmission  of    in- 
fections,  75 
Ameba,  varieties  of,  41 
Amyloid  degeneration,  328 
Anginas,  treatment  of,  662 
Anthrax,  intraplacental  transmission  of, 
581 

symptomatic,  toxin  of,  126 

toxin  of,  126 
Antipyrin,  action  of,  on  hectic  fever  of 
tuberculosis,  802 

use  of,  at  terminal  period  of  infec- 
tion, S03 
Antisepsis  of  alimentary  canal.  66S 

by  chemical  agents.  653 

general,  673 

of  genital  and  urinary  organs,  (iiil 

of  intestine,  672 

of  mouth,  662 

by  physical  agents.  652 

of  respiratory  passages,  665 

of  serous  membranes.  671 

of  skin.  659 
Antiseptics,  657 
Antithermics,  chemical,  801 
Antitoxinie  method,  675 
Aphasia.  409 


\  pparat  us,  circulator} . 
and    \ 1 1-  M'   . 
influence  ol  infeel  ion  -  upon.   1 13 
treatment  of  cardiovascular  mani- 
festations, 825 
Appcinlicit is.  experimental,  215 
\  rteries,  ad  ion  of  infeel  iong  upon,  153 
Axterioscleroc  is,  role  of  infeel  wmh   in  de- 
velopment of,   155 

Art  liropal  hies,    infect  ioUS,    I  Hi 

produced  by  scrum  injection-.  711 
Aspergillu  -  euro!  ium  repens,  W 

Savescens,  Ml 

fumigatus,   10 

oidulans,  10 

nigricans,  40 
Astringents,  791 

Autobactercinia,  2  17 

Autoinfections,  78,  92 

Autointoxication-.  78 


BACILLI,  37 
classification   ol 
Bacillus,  colon,  toxins  of,  L28 
of  glanders,  biology  of.  37  1 
septicus  putidus.  toxins  of,  127 
of  tuberculosis,  biology  of,  277 
Bacteria  accidentally  pyogenic,  190 
action  of  chemical  agents  on,  55 
of  heat  on.  53 
of  light  on,  54 
of  organic  fluids  on,  553 
of  pressure  on,  50 
of  serum  on  morphology  i      557 
anaerobic  pyogenic.  189 
classification  of.  37 
curved,  37 
determination  of.  43 
distribution   of,    within   normal    or- 
ganism. 7'.» 
general  characters  ■ 
importance  of  number  of,  in  the  de- 
velopment of  infection-.  98 
influence  of  various  external  agents 

upon.  50 
mode  of  action  of,  10S 
modes  of  entrance  of,  101 
non-specific,  classification  of,  ^v 
parasitic.  35 
passage  o\.  from  a  saprophytic  to  a 

pathogenic  life,  36 
pathogenic.  35  r 


55 


866 


INDEX. 


Bacteria,  polymorphism  of.  43 

pyogenic,  1S5 

relation  of,  to  algse,  35 

role  of,  in  development  of  infections, 

98 

saprophytic,  35 

search    tor   pathogenic,    by    micro- 
scopic examination   and  cultiva- 
tion, 607 
selective  injuriousness  of,  100 
specific,  classification  of,  39 

pyogenic,  190 
toxins  of,  120 
variability  of  functions  of,  46 

of  pathogenic  properties  of,  49 
variations  in  virulence  of,  99 
Bacterial  ferments,  47 

pigments,  variability  of,  47 
Bacteriology,  determinism  in,  61 
of  gaseous  gangrene,  232 
of  septicemia,  248,  258 
Bacteriotherapy,  681 
Balneotherapv.     See  Baths. 
Baths,  cold,  793 

lukewarm,  793 
Bicarbonate  of  soda,  influence  of,  on  pro- 
tective action  of  liver,  161 
Blood,  action  of  venous,  upon  tempera- 
ture, 350 
bacterioscopic  examination  of,  367 
microscopic  study  of,  363 
modifications  in,   catised  by  serum 
injections,  745 
of,  in  course  of  infections,  359 
protective  role  of,  761 
role  of,  in  thermal  regulations,  348 
toxicity  of,  in  some  infections,  132 
Blood-letting,  805 
Bone-marrow,  in  infections,  369 
lesions  of,  in  infections,  376 
modifications  of,  in  experimental  in- 
fections, 370 
normal  anatomy  and  phvsiology  of, 

369 
reactions  of,  in  man,  373 
semeiology  of,  377 
Bones,  infections  in,  440 
Bronchi,  457 
Bronchitis,  457 

varieties  of,  457 
Bubonic  plague,  immunity  against,  860 

serumtherapy  of,  707 
Buccopharyngeal  manifestations  in  scar- 
latina, 471 
in  smallpox,  472 
suppuration,  213 
Bulbar  manifestations,  411 


CALCIUM  chloride.      See  Chloride  of 
calcium. 
Calomel,  771 

Cancer,  inoculations  of,  321 
Cardiovascular     manifestations,     treat- 
ment of,  825 


Caustics,  790 

Cells,  degenerations  of,  324-3.T2 

Cephalalgia,  405 

in  infections,  405 
Cerebral  manifestations  in  infections,  404 
Chloride  of  calcium,  787 
Cholera,  crisis  in,  526 

immunity  against,  860 

serumtherapy  of,  700 

toxin  of,  125 
Choleriform  enteritis,  477 
Chorea,  425 

crisis  in,  526 

serumtherapy  of,  700 
Cinchona,  677 

Circulator}'  apparatus.     Sec  also  Heart 
and  Arteries, 
influence  of  infections  on,  443 
treatment     of     cardiovascular 
manifestations,  825 

disorders,  role  of,  in  gangrene,  230 
Clothing,  role  of,  in  transmission  of  in- 
fections, 74 
Cocci,  37 
Colon  bacillosis,  188 

serumtherapv  of,  702 
toxins  of,  128 
Coma,  408 

Contagion,  definition  of,  IS 
Convalescence,  527 

hygiene  of,  844 
Convulsions,  410 
Crises  in  cholera,  526 

in  chorea,  526 

definition  of,  518 

in  erysipelas,  524 

in  pneumonia,  521 

in  scarlatina,  525 

in  typhus,  524 

in  various  infections,  525 
Cultivation,  search  for  pathogenic  agents 

by,  607 
Cytologic  examination,  617 


dis- 


DEATH,  535 
Declaration    of     contagious 
eases,  845 
Degeneration  or  degenerations,  amyloid, 
328 
causes  of,  326 
cellular,  324-332 
fatty,  327 
pigmentary,  331 
varieties  of,  324-32(1 
Delirium,  406 

Determinism  in  bacteriology,  61 
Diagnosis  according  to  chemical  modifi- 
cations in  fluids,  623 
of  infectious  diseases,  606-631 
inoculation  from  the  point  of  view 

of,  613 
by  microbic  toxins,  624 
rules  of  clinical,  627 
by  therapeutics,  624 


INDEX 


867 


Diagnosis,  vesicatory  test  in,  81S 

Digestive  apparatus,    flee  all  o  Alimenl  - 
ary  canal  and  Stomach, 
infections  in,  169 
influence  <>r  infections  on,  169 
treatment  of  disorders  of,  831 

Diphtheria,  serumtherapy  of,  703 

Diphtheritic  paralysis,  l~o 

Diseases,  infectious,    flee  infection  . 

Dysenteriform  enteritis,  177 

l  )ysentery,  amebic,  176 
bacterial,  476 

Dystrophies,  of  infectious  origin,  598 


EAK,  auricular  suppural  ions,  21  I 
Embolism,  335 

Emunctories,  protect  ive  r. >l< •  of,  702 
Endocarditis,  449 

Undomyces  :illiic:i.!is,  \W.\ 

Ententes,  choleriform,  177 

dysenteriform,  177 
Epidemics,  67 

influence  of,  upon  prognosis,  633 
variations  of,   with   countries  and 
epochs,  96 
Epilepsy,  -425 
Ergot,  789 
Ergo  tin,  771 

Eruption,  relationship  between  intensity 
of  eruption  and  gravity  of  disease,  434 
Eruptive  fevers,  serumtherapy  of,  730 

transmission  of,  f>S<> 
Erysipelas,  crisis  in,  524 

treatment  of,  by  lukewarm  baths, 
S00 
Erysipelatous  paralysis,  422 
Erythemata,  mechanism  and  variability 

of  infectious,  439 
Etiological  conditions,  importance  of,  in 

diagnosis,  634 
Etiology  of  infections,  64-97 
Examination,  cytologic,  617 

microscopic,   search  for  pathogenic 
agents  by,  607 
Exanthemata,  431 

produced  by  serum  injections,  739 
Experimentation,  role  of,  in  study  of  in- 
fectious diseases,  58 
Exudates,  serous,  174 
Eye,  ocular  suppurations,  214 


FAMILY,  role  of,  in  infections,  86 
Farcina  bovidse,  39 
Fasting,   influence   of,   upon   protective 

action  of  liver,  160 
Fatigue,  influence  of,  on  infections,  94 
Fatty  degeneration,  327 
Febrile  manifestations,  treatment  of,  S19 
Fecal  matters,  toxicity  of,  116 
Ferments,  bacterial,  47 
Fetid  pleurisy,  240 
Fever  or  fevers,  33S 

caused  by  injection  of  serums,  741 


I  •    •!,  chara<  U  i 

Seal  ion  o 

deflnil  loi 

eruptive,    erumthcrap    ■ 

mechani  m  ol ,  3  W 

i .,i'  of  blood  i' 

■  meiological  \  .•  1 1 1 1 « ■  of, 

i  berap  ul  ic    of,  7!»2 

typhoid,  auto 

clinical  form   of,  516 
coni  vindications  of  cold 
i  1 1  tr  in,  < 

1 1 1 1 1  r  1 1 1 1 1 1 1 

erumthei  729 

to  in  of,  131 
Fluids,   organic,    flee   also    Blood    and 

iin. 
.ici ion  of,  on  bacteria,  G 
modifical  ions  in,  •''.•'>7 
various,  employed  in  thi  i 
tics,  697 
Food.     Sec  also  Alinnni  -. 

role  of,  in  the  transmission  of  infec- 
tions, 7.", 
Fungi,  infectious,  39 


GALLING,  tuberculosis  of,  290 
Gangrene,  225-243 
Gangrene,  causes  favoring  development 

*     of,  227 
definition  of,  227 
gaseous,  bacteriology  of,  232 
toxin  of,  126 
various  agents  of,  2:w 
of  limbs,  235 
of  liver,  241 
of  lungs,  238 
of  mammary  glands,  235 
principal  agents  of,  232 
pulmonary,  238 
role  of  chemical  agents  in,  230 

of  circulatory  disorders  in,  230 

of  intoxications  in,  231 

of    mechanical    and    phvsical 

agents  in,  229 
of  nervous  system  in,  231 
of  spleen,  241 
treatment  of,  781 
in  various  parts  of  organism.  235 
Gangrenous  lesions,  treatment  of,  781 

pleurisy,  240 
Gastrointestinal   putrefactions,   114-120 
Generation,  spontaneous,  34 
Genital  organs,  antisepsis  of,  661 
Genito-urinarv  organs,  antisepsis  of,  661 
gangrene  of.  241 
infection  by,  106 
influence  of  infections  on,  490 
suppurations  of,  221 
Germicidal  substances,  role  of  spleen  in 

production  of.  3S1 
Glanders,  animals  sensitive  or  refraetory 
to,  275 


868 


IXBEX. 


Glanders,  bacillus  of,  biology  of,  374 

etiology  of,  275 

pathological  anatomy  of,  276 

serum  therapy  of,  709 

toxins  of,  131 
Glucose,  influence  of,   upon  protective 

action  of  liver,  160 
Guaiacol,  804 


HEART.     See  also  Myocarditis,  En- 
docarditis, and  Pericarditis. 

action  of  toxins  upon,  444 

functional  disorders  of,  443 

post-infectious  hypertrophy  of,  448 
Hemiplegia,  409 

Hemorrhages,    caused   by   injections   of 
serum,  744 

causes  of,  general,  785 
local,  783 

therapeutic  indications  of,  780 

treatment  of,  783 
Hemorrhagic  pleurisy,  467 

septicemia,  245,  255 
Heredity,  580-605 
Heterointoxications,  64 

of  gastrointestinal  origin,  118 
Humoral     modifications    of    lymphatic 

origin,  387 
Hydrocele,  776 
Hydrophobia,  serumtherapy  of,  735 

vaccination  against,  855 
Hygiene  of  convalescence,  844 

individual,  837 

of  sick,  840 

of  sick  room,  837 

social,  845 
Hyperthermia,  33S 


IMMUNITY,  acquired,  559 
congenital,  599 
individual,  88 
mechanism  of,  551-579 
natural,  557 
Immunization  against  cholera,  typhoid 
fever,  and  bubonic  plague,  860 
by  attenuated  viruses,  854 
by  means  of  strong  viruses,  847 
Incubation,  495 

importance  of  duration  of,  in  prog- 
nosis, 635 
period  of,  22 
Infantile  paralysis,  417 
Infection  or  infections,  abortive,  512 
action  of,  on  organs  of  sense,  428 
of  poisons  upon,  91 
of,   on    respiratory   apparatus, 
456 
autogenic  origin  of  various  specific, 

81 
bones  in,  440 
cephalalgia  in,  405 
circulatory  apparatus  in,  443 
classification  of,  24 


Infection,  clinical  forms  of,  511 
combined,  142 

in  alimentary  canal,  148 

in  respiratory  apparatus,  147 

of  skin,  145 

of  throat,  145 
consequences  of,  541-550 
cutaneous  manifestations  in,  429 

origin,  102 
declaration  of,  8  15 
definition  of,  24 

diagnosis  and  prognosis  of,  600-641 
digestive  apparatus  in,  469 
eruptive,  26 
etiology  of,  64-97 
evolution  of,  494-540 
history  of,  30 

hygiene  and  prophylaxis  of,  537-863 
incubation  of,  495 
individual  immunity  from,  SS 

predisposition  to,  88 
influence  of'  age  on,  88 

of  autoinfections  on,  92 

of  family  on,  86 

of  fatigue  and  overwork  on,  94 

on  genital  organs,  490 

of  individuals  on,  88 

on  neuropathies,  427 

of  poisons  on,  91 

of  seasons  on,  84 

of   sex  and   age  on  frequency 
of,  89 
intraplacental        transmission       of 
chronic,  593 

of  human,  583 
invasion  of,  503 
lesions  of  bone-marrow  in,  376 
lymphatic  glands  in,  382 
meaning  of,  17 
miasmatic,  18 

modifications  of  blood  in  course  of, 
359 

bone-marrow  in  experimental, 
370 
muscular  system  in,  438 
nervous  system  in,  403 
neuroses  following,  423 
non-specific,  29 

passage  of  acute  to  a  chronic  condi- 
tion, 531 
pathogenesis  of,  98-134 
role  of,  in  development  of  arterio- 
sclerosis, 455 

of,  in  development   of  general 
paralysis,  408 
secondary,  144 

simultaneous  occurrence  of  two,  143 
specific,  25,  29 
spinal  cord  in,  412 
spleen  in,  378 
stationary  period  of,  506 
suprarenal  capsules  in,  400 
termination  of,  516 
therapeutics  of,  642-836 
through  alimentary  canal,  105 


INDEX 


Infection  through  genito  urinarj  organs, 

100 

nervous  system,  L06 
organs  of  sense,  1 06 
respiratory  pa  sages.  103 
.serous  membrane  i,  106 
\  ascular  system,  1 07 
thymus  in,  387 
thyroid  gland  in,  393 
i  ransmission  of.  by  contact,  65 
through  aliments,  75 
air,  69 
(•In!  hin^,  7  I 
invertebrates,  !'■'< 
plants,  7  I 

by  soil,  72 

by  water,  71 
tumors  and,  :il  !> 
venereal,  27 
virulent,  31 

with  nodular  productions,  2.x 
with  septicemic  tendency,  27 
Infectious  agents,  action  of,  ~\ 
classifical  ion  of,  35 
mode  of  en1  ranee  of,  101 
Inflammatory   exudates,    treatment  of, 
772 
manifestations,  treatment  of,  765 
Infusoria,  :!  I 

Inoculation  or   inoculations.     Sec,  also 
Vaccination. 
of  actinomyces,  316 
of  cancer,  321 

from  a  diagnostic  standpoint,  013 

subcutaneous,  102 

of  tuberculosis,  288 

Insanity  in  tuberculosis,  407 

Intestine,  antisepsis  of,  072 

choleriform  and  dysenteriform  affec- 
tions of,  177 
disturbances  and   lesions  of,  in  in- 
fections, 474 
Intoxications,  role  of,  in  gangrene,  231 
Intraplacental  transmission  of  anthrax, 
581 
of  chronic  infections,  593 
of  human  infections,  5S3 
Invasion,  503 

importance  of  mode  of,  in  diagnosis, 
635 
Invertebrates,  role  of,  in  transmission  of 

infections,  73 
Iodine,  67S 
Ipecac,  790 


I, .pro  ■  1 1 1 1  >  1 1 1,.  ■i:i|,-    .,|     70'i 

Leptotnrix,  37 
I.,    ion  or  li 

local,  role  of,   in     uppir 

108 
reparat  ion  ol  •  raumal  ic  and  a 

infect  iou  .  5 1 1   ■"•  15 
uppurat  ing,  generalizat  ion  i 
Leucoi    U        ■•  364 

Limb 

Liver,  aoHct     i     •  ■     220 
act  ion  "i .  on  micro 
gangrene  of,  211 
general  charactei    ol  in  1 
influence  ol  bicarbonate  ol  raids,  on 
protect  ive  act  ion  ol .  161 
>.i   fasting  upon  protect 

lion  of,  160 
of  glucose  upon  protect 

1  ion  ol .  160 
of  infect  iouf  di  -•■■'  • 
protect i\ e  rdle  of,  l">r>.  1 59    ■ 
role  of,  iii  1  hermogenesis,  351 
semeiology  of  infection-.  ts7 
Lungs.     See  also  Respirator  apparatus, 
classification  of  lesions  of,  of  infec- 
tious origin,  160 
gangrene  of,  238 
in  infect ioua  diseases,  i".n 

normal  physiology  of,   158 
protect  i\  e   role  of,    1 56,   760 

role  of,  in  thermogenesis,  351 
Lymphatic  glands,  histological  stud 
384 

in  infect  ions,  382 
inflammation  of,  in  variola.  386 
protective  rdle  of,  1">1 


of, 


K 


IDNEYS,  influence  of  infectious  on, 

4S9 
role  of,  in  thermogenesis,  351 

treatment  of  renal  disorders,  835 


T  ACTATION,   influence  of   infections 


on, 491 
Larynx  in  infections,  456 


MALLEIX,  625,  694 
Mammary    glands,   gangrene 

235 

Measles,  buccopharyngeal  manifestations 
in,  470 

Medication,  depletive.  ,71 

physiological,  757 

specific.  676 

symptomatic,  S19 

vasomotor,  771 
Meningitis,  infectious,  426 
Menstruation,  influence  of  infections 

490 
Mercury.  07s 
Meteorological    influence   on    infect 

84 
Miasmatic  diseases,  L8 
Microbes.     See  also  Bacteria. 

association  of,  135-153 

modifications  of  action  of  liver  upon. 
159 

necrosing  role  of  pyogenic.  234 

passage  of,  through  placenta.  580 

toxins  of  pyogenic.  129 
Microbie  associations.  135-153.  10<> 

products,  favorable  to  infection.  137 


870 


fXDEX. 


Milk,  passage  of  active  substances  into, 
568 
role  of,  in  the  transmission  of  infec- 
tions, 75 
Mouth,  antisepsis  of,  602 

buccopharyngeal   manifestations  in 
measles,  470 
in  scarlatina,  471 
in  varicella,  472 
in  variola,  472 
in  various  infections,  472 
Murmurs,  non-organic,  of  heart,  443 
Muscles  or  muscular  system  in  infections, 

43S 
Mycoses  in  man,  319 
Myelitis,  414 

in  various  infections,  417 
Myocarditis,  acute,  446 


"VTEPHRITIS  caused  by  serum  injec- 
1M      tions,  742 
Nervous  connections,  337 

manifestations,  treatment  of,  821 
system,  connections  of,  337 
infection  through,  106 
in  infections,  403 
role  of,  in  development  of  gan- 
grene, 231 
nervous  alterations  in  sup- 
puration, 197 
suppuration  of,  222 
treatment  of  manifestations  of, 
821 
Neurites,  419 
Neuropathies,  influence  of  infections  on, 

427 
Neuroses  following  infections,  423 

post-infectious,  423 
Nocardia  farcinosa,  39 
Nodular  infections,  272-322 

lesions,  treatment  of,  783 
Nose,  nasal  suppurations,  213 


OBNUBILATION,  408 
Oidiomycosis.     See  also  Endomy- 
cosis. 
biology  of  parasite  of,  302 
experimental,  307 
histological  study  of,  309 
nature  of,  312 
Oidium  albicans,  302 

characters  of  cultures  of,  304 
role  of,   in   human  pathologv, 
304 
Omentum,  protective  role  of,  154 
Oomyces,  40 
Oospora  asteroides,  39 
Organism,  defenses  of,  154,  181 

influence  of  infections  on,  359-493 
reactions  of,  against  infections,  166 

inflammatory,  168 
return  of,  to  a  former  state  of  its 
evolution,  549 


Organism,  suppuration  in  various  parts 

of,  212 
Organs.     See  also  Tissues  and  Cells. 

action   of   various,    upon   microbic 

poisons,  164 
contiguity  of,  334 

modifications  of  hematopoietic,  368 
of  sense,  action  of  infections  on,  428 
infection  by,  106 
Osteopathies,  infectious,  440 
Overwork,  influence  of,  upon  infections, 
94 


PANCREAS,  action  of  infections  on, 
488 
suppurations  of,  221 
Paralysis  or  paralyses,  acute  ascending, 
'  414 

diphtheritic,  420 
erj'sipelatous,  422 

general,  role  of  infections  in  develop- 
ment of,  408 
infantile,  417 
scarlatinal,  422 
Parasites  capable  of  inducing  suppura- 
tion, 183 
pyogenic,  animal,  192 

relative  frequency  of,  193 
vegetable,  191 
Parasitic  agents,   action  of,  23 
Parrots,  tuberculosis  of,  293 
Pathogenesis  of  infections,  98-134 
Pathogenic  agents,  mode  of  action  of, 
108 
of  entrance  of,  101 
search  for  bjr  microscopic  ex- 
amination and  cultivation, 
607 
selective  injuriousness  of,  100 
Pericarditis,  452 
Peritonitis,  tubercular,  775 
Peroxide  of  hydrogen  in  treatment  of 
gangrene,  781 
of  hemorrhages,  792 
Perspiration,  437 
Phycomyces,  40 
Pigmentary  degeneration,  331 
Pigments,  bacterial,  variability  of,  47 
Placenta,  intraplacental  transmission  of 
chronic  infections,  593 
passage  of  microbes  through,  580 
Plants,  role  of,  in  transmission  of  infec- 
tions, 74 
Plasmodium  malaria?,  42 
Pleura,  lesions  of,  in  infections,  465 
Pleurisy  or  pleurisies,   gangrenous  and 
fetid,  240 
hemorrhagic,  467 
purulent,  467 
serous,  465 
treatment  of,  772 
Pneumococcosis,  serumtherapy  of,  710 
Pneumococcus,  187 
toxin  of,  130 


INDEX. 


871 


Pneumonia,  clinical  forma  of,  515 

crisi.s  in,  .r>2l 

Poisons.    See  also  Ptomainsand  Toxins, 
action  of,  on  infections,  91 
liver  on,  I  62 
of  various  organs  on  microbio, 

Kil 

defenses  of  organism  against)  162 
found  in  infected  organism  i,  1 8 1 
tnicrobic,  10!' 
ptomain,  1 13 
putrid,  L09 
Predisposition.  88,  551  679 

congenital,  599 
Pregnancy,   influence  of  infections  on, 

mi 
Prognosis,  bases  of,  at  stationary  period, 
635 
general  rules  of,  <>:{!) 
importance  <>i  duration  of  incuba- 
tion and  of  mode  of  invasion  in, 
i>;?.r) 
of  infectious  diseases,  631 
influence  of  age  on,  632 
of  epidemics  on,  633 
of  se\  on,  <>:w 

of   serumtherapy  accidents,   717 

Prophylaxis  by  serum,  861 
Proteobacillosis,  serumtherapy  of,  712 

Protozoa,  infectious,  41 
Pseudomembranes,  176 

diphtheritic,  177 
I  Veiidomcmbranous  exudates,  treatment 

of,  781 
1  'seudotuberculosis,  295 

by  animal  parasites,  bacterial,  29S 
human,  301 
micotic,  297 

by  inanimate  substances,  295 
Ptomains.     Sec  also  Poisons  and  Toxins. 

table  of,  113 
Pulmonary  gangrene,  238 
Purulent  exudates,  treatment  of,  777 

foci,  development  and  evolution  of, 
20S 

pleurisy,  467 
Pus.     See  also  Suppuration  and  Puru- 
lent Foci. 

physical  and  chemical  characters  of, 
204 
Putrefactions,  gastrointestinal,  114-120 
Pyemia.     See  also  Septicemia. 

of  animals,  255 

attenuated  form  of,  264 

clinical  evolutions  of,  261 

distinction  of,  from  septicemia,  244 

experimental,  250 

history  of,  251 

human,  257 

relationship    between    variola    and, 
265 

relative  frequency  of  agents  of,  260 

of  saprophytic  origin,  254 
Pyocyanobacillosis,  serumtherapy  of.  712 
Pvramidon.  S03 


/   |HMM 


RABBI]  -.  epizootic  purulent  rhinitis 
of,  256 
<  cperimental  \  ariola  ol 
[label's  water,  786 
Rabie  ,    .-<  ■    n  drophobia. 

n'.le  of,  in  infei 
Eleactions,  general,  333 
Recurrences,  630 
Relapses,  52!) 

Renal  di  ordi  r  ,  I  reatmenl  of, 
Re  piratorj  apparat u      Bet    ■•  •■  ] >ungs. 
action  of  infection!  on,  156 
ant  i  ep  i    of,  665 
combmed  infection*  in,  I  17 

ill  hi. I'  r    of,    WO 

remote  consequence*  of  infec- 

i  w  e  lesiom  ol .  168 
nippural  ion  of,  214 
manifestal  ions  in,  827 
passages,  antisepsis  of,  665 
infections  through,  103 
Rhatania,  791 


QALICYLIC  acid,  680 
O     Scarlatina,  buccopharyngeal  mani- 
festations in,  1-1 
crisis  in,  525 
Scarlatinal  paralysis,  422 
Season,  influence  of,  in  infect  inns.  84 
Secretions,  passage  ol  activi    -  ibst  n 
into,  568 
sudoral,  437 
Septicemias  of  animals,  255 
attenuated  forms  of,  2f>l 
bacteriology  of,  248 
classification  of,  246 
clinical  evolution  of,  261 
definition  of.  244 
experimental,  250 
hemorrhagic,  245.  255 
history  of,  251 
human,  257 

bacteriology  of.  258 
of  intestinal  origin.  254 
of  nasal  origin.  253 
principal    agents   of   spontaneous, 

249 
relationship    between    variola    and, 

265 
relative  frequency  of  agents  0 
of  salivary  origin.  253 
of  saprophytic  origin,  254 
secondary,  149 

localizations  of,  151 
Serous  exudates,  treatment  of,  772 
membranes.     See  also  Omentum. 
antisepsis  of,  671 
infection  through.  106 
suppurations  of,  222 
pleurisy,  465 


872 


INDEX. 


Serum   or    serums.       See    also    Serum- 
therapy. 
accidents  ascribable  to  injections  of, 

739,  746 
action   of,   on    morphology  of    mi- 
crobes, 557,  500 
of,  on  virulence,  557 
agglutinating  power  of,  501 
antitoxic  properties  of,  50-4 
artificial,  injections  of,  SOS 

indications  for,  S14 
attenuating  power  of,  562 
mode  of  action  of  therapeutic,  751 
modification  of,  in  acute  diseases, 
574 
of,  in  animals  predisposed  to 
infections,  572 
nature  and  origin  of  various  active 

substances  contained  in,  577 
prophylactic  injections  of,  737 
prophylaxis,  801 
Serumtherapy,  094 

accidents  ascribable  to,  739 

of  bubonic  plague,  709 

causes  and  mechanism  of  accidents 

of,  749 
of  cholera,  700 
of  chorea,  700 
of  colon  bacillosis,  702 
of  diphtheria,  703 
of  eruptive  fevers,  730 
of  glanders,  709 
of  hydrophobia,  735 
of  infections  whose  agents  are  not 

well  known,  730 
of  leprosy,  709 
mode  of  action  of,  751 
of  pneumococcosis,  710 
of  proteobacillosis,  712 
of  pyocyanobacillosis,  712 
of  smallpox,  733 
of  staphylococcosis,  713 
of  streptococcosis,  714 
of  svphilis,  730 
of  tetanus,  722 
of  tuberculosis,  724 
of  typhoid  fever,  729 
of  vaccinia  and  variola,  133 
various  applications  of,  700 
Sex,  influence  of,  upon  prognosis,  033 

role  of,  in  infectious  diseases,  88 
Silkworm  disease,  34 
Skin,  antisepsis  of,  059 

combined  infections  of,  145 
consequences    of    cutaneous    infec- 
tions, 436 
cutaneous   manifestations  in  infec- 
tions, 429 
suppurations,  213 
Smallpox,  adenopathies  in,    386 

buccopharyngeal  manifestations  in, 

472 
congenital,  586 
cultivation  of  microbe  of,  269 
epidemiology  of,  67 


Smallpox,  microbiology  of,  267 

relation  of,  to  septicemia  and  pye- 
mia, 265 

serumtherapy  of,  733 
Specific  medication  or  treatment,  670 
Spinal  cord  in  infections,  412 
Spleen,  gangrene  of,  241 

in  infectious  diseases,  378 

role  of,  in  production  of  germicidal 
substances,  3S1 
Sporozoa,  41 

Staphylococcosis,  serumtherapy  of,  713 
Staphylococcus,  185 
Stationary  period,  500 

bases  of  prognosis  at,  035 
Sterilization  of  morbid  products,  S39 
Stomach,  action  of  infections  on,  473 
Stomatitis,  treatment  of,  002 
Streptococcosis,  serumtherapy  of,  714 
Streptococcus,  ISO 
Streptothrix,  pathogenic,  318 
Suckling  by  infected  women,  492 
Sudoral  secretions,  437 
Suette  picarde,  90 

Suppuration,    182-224.     See    also    Pus 
and  Purulent  Foci. 

auxiliary  causes  of,  195 

buccopharyngeal,  213 

cold,  212 

of  nervous  system,  222 

non-microbic,  201 

in  clinical  observations,  203 

parasites  of,  184 

of  respiratory  apparatus,  214 

role  of  general  state  in  suppurative 
processes,  199 
of  microbic  products  in,  203 

in  various  parts  of  organism,  212 
Suprarenal  capsule,  infections  in,  400 
Sweat,  437 

Sympathies,  morbid,  333 
Symptomatic  anthrax,  toxin  of,  120 
Synergies,  functional,  333 
Syphilis,  adenopathies  in,  380 

serumtherapy  of,  730 


TANNIN,  791 
Tartar  emetic,  771 
Temperature,  action  of  microbic  toxins 
on,  341 
daily  course  of  rectal,  under  normal 

conditions,  350 
semeiological  value  of  course  of,  358 
Termination  of  infections,  510 
Tetanus,  serumtherapy  of,  722 

toxin  of,  124 
Tetany,  425 

Tetracoccus  buccalis,  44 
Therapeutics,  antiseptic  method  of,  052 
antitoxinic  method  of,  075 
bacteriotherapic  method  of,  081 
diagnosis  by,  024 
of  fever,  792 
general  rules  of,  in  infections,  048 


in  in:. \. 


873 


Therapeutics  of  infectious  dises  e  i,  (>I2 
836 
physiological,  7.r>x 
serumtherapic  mel  hod  of.  69 1 
specific  medication  in,  070 
various  organic  Quids  employed  in, 
697 
Thermogenesis,  rdle  of  kidneys  in,  351 
of  li  \<i-  in,  361 
oi  Lungs  in,  361 
Thoracentesis,  772 

rules  of,  7715 
Throat,  com!  lined  infecl  ions  i  if,  I  16 
Thymus,    histological    modification 
in  infections,  390 
in  infections,  387 
primary  infection  of,  393 
Thyroid  glands,  experimental  tumors  of, 
320 
general  characters  of,  in  acute 

infecl  ions,  396 
in  infecl  ions  diseases,  393 
mechanism  and  significance  ol 

lesions  of,  398 

normal  histology  of,  39  I 
Tissues.     See  also  ( Irgans. 

germicidal  properties  of,  509 

Toxicity  of  fecal  nial  lers,  1 1(> 

Toxins,  action  of  microbic,  upon  tem- 
perature, 341 
of,  upon  organism,  1 22 
of  tubercular,  287 
of  cholera,  125 
description  of  principal,  12:; 
diagnosis  by  microbic,  624 
of  gaseous  gangrene,  L26 
of  glanders,  131 
modes  of  elimination  of,  164 
of  pathogenic  microbes,  120 
of  symptomatic  anthrax,  120 
of  tetanus,  124 

of  tuberculosis,  actions  of,  287 
of  typhoid  fever,  131 
Trachea,  457 

Tracheobronchial  adenopathies,  407 
Transmission  of  eruptive  fevers,  580 
intraplacental,  of  anthrax,  581 
of  tuberculosis  by  contact,  08 
by  inhalation,  70 
Treatment.     See    also    Medication    and 
Therapeutics. 
of  anginas,  002 

antiseptic,    of    stomatites   and    an- 
ginas, 662 
of     cardiovascular     manifestations, 

825 
by  cold  applications,  790 
b>r  depletion,  708 
of  digestive  disorders,  831 
of  disorders  of  digestive  apparatus, 

831 
of  erysipelas,  800 
of  febrile  manifestations,  819 
of  gangrene,  7S1 

peroxide  of  hydrogen  in,  7S1 


[Veal 1 1 i'ii i  oi  hen 

peroxidi  ■ 
li-   hot  applical  ion 
by  immobilizat  ioi 
'.i  inflammatoi  •.  i    udate  i,  772 

manife  tal  ion 
b)    injection     ol    artifi( 

SOS 

local,  766 

oi  nen  ou    mai 

oi  Qodulai  li 

of  pleuri  \ -,  772 

ni     pseuaomembrai 

7S 
ni  purulenl  exudate 
l,v  refrigeral ion,  766 

OI  renal  di  ord<  i 
of  respiratory  man  i 
by  re,  ni   inii.  768 

oi  Berous  exudate   .  772 

of  stomal  il  is,  662 

by  t  horacentesis,  77:; 

by  \  enesection,  806 
Drichinosis,  42 
Tubercle,  evolul  ion  of,  286 

histo  .  283 

histological  study  of  oidian,  3 
Tubercular  adenopal  hies,  386 

insanity,  107 

peritonitis,  775 
Tuberculin.  688 
Tuberculosis.     See  also  rubercle. 

of  animals,  289 

bacillus  of,  biology  ol .  277 

el  iology  of,  27(.i 

of  gallina.  290 

inOculabihty  of,  2vs 

insanity  in,  407 

pathological  anatomy  oi .  280 

pseudo-,  295 
of  psittaci,  293 
serumtherapy  of,  72 1 
toxins  of.  action  of,  287 
transmission  of,  by  contact,  08 

by  inhalation.  70 
vesicatory     test     in     diagnosis    of. 
621 
Tumors  and  infections.  319 

experimental,     of     thyroid     gland. 
320 
Typhoid  fever,  autogenic.  v2 
clinical  forms  of.  510 
contraindications  of  cold  bath- 
ing in,  795 
immunity  against,  S 
serumtherapy  of,  ~- 
toxin  of.  131 
Typhus,  crisis  in.  .V24 


URINARY  organs,  antisepsis  oi.  661 
Urine,  modifications  oi.  produced 
by  serum  injections.  742 
toxicity  of, in  some  infections. 
132  " 


874 


IXBEX. 


VACCINIA,  serumtherapy  of,  733 
Vaccination  against  hydrophobia, 
855 
the  oidium,  309 
of  animals,  696 
antivariolar,  849 
dangers  of,  861 
prophylactic,  S46 
Varicella,    buccopharyngeal    manifesta- 
tions in,  472    - 
Variola.     See  Smallpox. 

buccopharyngeal  manifestations  in, 

472 
relationship   between   pyemia   and, 
265 
septicemia  and,  265 


Variola,  serumtherapy  of,  733 
Vascular  connections,  335 

system,  infections  through,  107 
Venesection,  805 
Vesicatory  test,  618 
Virulence,  action  of  serum  upon,  557 

variations  of,  99 
Visceropathies,  post-infectious,  545 

role  of  previous,  in  prognosis,  638 

"VTEASTS,  pathogenic  role  of,  313 


z 


YGOMYCES,  40 


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DUANE  (ALEXANDER).  A  DICTIONARY  OF  MEDICINE  AND  THE 
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ESSIG  (CHARLES  J.).  PROSTHETIC  DENTISTRY.  Second  Edition.  See 
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FARQUHARSON  (ROBERT).  A  GUIDE  TO  THERAPEUTICS.  Fourth 
edition,  revised  by  Frank  Woodbury,  M.D.     12mo.,  581  pages.     Cloth,  $2.50. 

FIELD  (GEORGE  P.).  A  MANUAL  OF  DISEASES  OF  THE  EAR.  Fourth 
edition.     Octavo,  391  pages,  with  73  engravings  and  21  colored  plates.     Cloth,  $3.75. 

FINDLEY  (PALMER  D.).  A  TREATISE  ON  GYNAECOLOGICAL  DIAG- 
NOSIS. Octavo,  493  pages,  210  engravings,  45  plates  in  black  and  colors.  Cloth, 
$4.50;  leather,  $5.50,  net.     Just  Ready. 

FLINT  (AUSTIN).  A  TREATISE  ON  THE  PRINCIPLES  AND  PRACTICE 
OF  MEDICINE.  Seventh  edition,  thoroughly  revised  by  Frederick  P.  Henry,  M.D. 
In  one  large  8vo.  volume  of  1143  pages,  with  engravings.     Cloth,  $5 ;  leather,  $6. 


Philadelphia,  706,  708  and  710  Sansom  St.— New  York,  111  Fifth  Avenue. 


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FLINT  (AUSTIN).     A   PRACTICAL    TREATISE  OH  THE  El 

edition,  enlarged.    Octavo,  550  pages.    <  ioih,$4. 

MEDICA  h  ESSA  YS,     in  one  L2mo.  volume  of  210  page  ,    I   • 


ON  THE  CHEST  AND  RESPIRATORY  ORQA  V, 

edition.    (  tetavo,  593  page  ,    I  Hoi  at  \  L50. 

ON  PHTHISIS,     in  one  8vo.  volume  of  142  page  ,    Clol 


FOLSOM  (C.  P.).    AN  ARSTRAOT  OF  STATUTES  OF  U.  8   0  VODJ 

OF  THE  INSANE,     tn  one  8vo.  volume  of  108  |  ith^  $1.60. 

FORMULARY,  THE  NATIONAL.    Bee  National  l>  14. 

FORMULARY,  POCKET.     Fifth  edition,    See]  ■'. 

FOSTER  (MICHAEL).  A  TEXT-ROOK  OF  PHYSIOLOGY.  3ixth  and  reviaed 
edition.    Octavo,  928  pages,  with  257  illustrations.    Cloth,  $4.50;  leathei 

FOTHERGILL  (J.  MILNER).    HA  NJD  BOOR  OF  TREA  TM1 
Octavo,  664  paged     Cloth,  $8.75;  leather,  $4.76. 

FOWNES    (GEORGE).     A    MANUAL    OF    ELEMENTARY    GHEMIS'a 
Twelfth  edition.     Embodying  Watts'  Physical  and  Tnorgame  Chemistry.     Boval  L2mou, 

lOlil  pages,  with  108  engravings,  and  1  colored  plate.     Cloth,  $2.75;  leather,  $8 

FRANKLAND  (E.)IAND  JAPP  (F.  R.).'-  INORGANIC  CHEMISTRY.    Octavo, 
677  pages,  with  51  engravings  and  2  plates.     Cloth,  $8.75;  leather,  $4. 76. 

FULLER  (EUGENE).  DISORDERS  OF  THE  SEXUAL  ORGANS  IN  THE 
MALE.     Octavo,  238  pages,  with  25  engravings  and  8  plates.     Cloth,  $2. 

GALLAUDET  (BERN  B.).  \A\POCKET  TEXT-BOOK  OF  SURGERY. 
12mo.  of  about  500  pages,  with  many  illustrations.  In  Press.  Led! s  Series  of  Pocket 
Text-Books.     Page  12. 

GANT  (FREDERICK  JAMES).  THE  STUDENT'S  SURGERY.  A  Multum  in 
Parvo.     In  one  square  octavo  volume  of  845  pages,  with  159  engravings.     Cloth,  $3.75. 

GAYLORD  (HARVEY  R.)   AND  ASCHOFF   (LUDWIGl    PATHOLOGICAL 

HISTOLOGY.     With  introductory  note  by  William  H.  WEi.cn,  M.D.     Quarto,  354 
pages,  with  81  engravings  and  40  full-page  plates.     Cloth,  -$7.50,  net. 

GERRISH  (FREDERIC  H.).  A  TEXT-BOOK  OF  ANATOMY.  By  American 
Authors.  Edited  by  Frederic  H.  Gerrish,  M.D.  Second  edition.  Imp.  octavo, 
937  pages,  with  1003  illustrations  in  black  and  colors.  Cloth,  $6.50;  sheep,  $7.50,  net; 
half  morocco,  $8.00,  net 

GIBBES  (HENEAGE).  PRACTICAL  PATHOLOGY  AND  MORBID  HIS- 
TOLOG  Y.   Octavo  of  314  pages,  with  60 illustrations,  mostly  photographic.   Cloth,  $2.75. 

GRAY  (HENRY).  ANATOMY,  DESCRIPTIVE  AND  SURGICAL.  Fifteenth 
edition,  thoroughly  revised.  In  one  imperial  octavo  volume  of  1249  pages,  with  780  large 
and  elaborate  engravings.  Price  with  illustrations  in  colors,  cloth.  $6.25,  net;  leather, 
$7.25,  net.     Price,  with  illustrations  in  black,  cloth,  $5.50;  leather,  $6.50,  net. 

GRAYSON  (CHARLES  P.).  DISEASES  OF  THE  THROAT.  NOSE,  AND 
.  1 SSOC  L I  TED  AFFECTIONS  OF  THE  E.  I R  Octavo.  548  pages,  with  129  engrav- 
ings and  8  plates  in  colors  and  monochrome.     ( Sloth,  *3.50,  net. 

GREEN  ( T.  HENRY).  PATHOLOGY  AND  MORBID  ANATOMY.  Ninth 
revised  edition.  Octavo,  565  pages,  with  330  engravings  and  4  colored  plates.  Cloth, 
$3.25.  ini. 

GREENE  (WILLIAM  ^.  MEDICAL  CHEMISTRY.  12mo..  310  pages,  with 
74  illustrations.     Cloth,  $1.75. 


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8  LEA     BROTHERS    &     C  0 .'  S    PUBLICATIONS. 


GRINDON    JOSEPH).     A    POCKET   TEXT-BOOK   OF  SKIN  DISEASES. 

12ruo.   of  367  pages,  with  39  illustrations.     Cloth,  S2.00;   flexible  leather,  $2.50,  net. 
Lea's  Series  of  Pocket  Text-Books.     Page  12. 

GROSS  iSAMUEL  D.).  THE  URINARY  BLADDER,  THE  PROSTATE 
GLAND  AND  THE  URETHRA.  Third  edition,  revised  by  Samuel  W.  Gross, 
M.D.     Octavo  of  574  pages,  with  170  illustrations.     Cloth,  $4.50. 

GUENTHER  (A.  E.  AND  T.  C).  AN  EPITOME  OF  PHYSIOLOGY.  12mo., 
225  pages,  illustrated.    Cloth,  $1.00,  net.    Lea's  Series  of  Medical  Epitomes.     See  page  10. 

HAJBERSHON  (S.  0.).  DISEASES  OF  THE  ABDOMEN.  Second  American  from 
the  third  English  edition.     Octavo,  554  pages,  with  11  engravings.     Cloth,  $3.50. 

HALL  (WINTIELD  S.).  TEXT-BOOK  OF  PHYSIOLOGY.  Octavo,  672  pages, 
with  343  engravings  and  6  colored  plates.     Cloth,  $4.00,  net;   leather,  $5.00,  net. 

HAMILTON  ( ALLAN  McLANE).  NERVOUS  DISEASES.  Second  and  revised 
edition.     Octavo,  598  pages,  with  72  engravings.     Cloth,  $4. 

HARD  A  WAY  (W.  A.).  MANUAL  OF  SKIN  DISEASES.  Second  edition. 
12mo.,  560  pages  with  40  illustrations  and  2  colored  plates.     Cloth,  $2.25,  net. 

HARE  (HOBART  AMORY).  A  TEXT-BOOK  OF  PRACTICAL  THERAPEU- 
TICS, with  Special  Reference  to  the  Application  of  Remedial  Measures  to  Disease  and 
their  Employment  upona  Rational  Basis.  Ninth  revised  edition.  Octavo,  851  pages, 
105  engravings,  4  colored  plates.  Cloth,  $4.00,  net;  leather,  $5.00,  net;  half  morocco, 
$5.50,  net. 


PRACTICAL  DIAGNOSIS.  The  Use  of  Symptoms  in  the  Diagnosis  of  Dis- 
ease. Fifth  edition,  revised  and  enlarged.  Octavo,  727  pages,  with  236  engravings, 
and  25  full-page  plates.     Cloth,  $5.00  ;  leather,  $6.00  ;  half  morocco,  $6.50,  net. 

Editor.     A  SYSTEM  OF  PRACTICAL  THERAPEUTICS.     By  American 


and  Foreign  Authors.  Second  edition.  In  three  large  octavo  volumes  containing  2593 
pages,  with  457  engravings  and  26  full-page  plates.  Price  per  volume,  cloth,  $5.00, 
net;  leather,  $6.00,  net;  half  morocco,  $7.00,  net.  For  sale  by  subscription  only.  Full 
prospectus  free  on  application  to  the  publishers. 

ON  THE  MEDICAL  COMPLICATIONS  AND  SEQUELAE  OF  TYPHOID 

FEVER.    Octavo,  276  pages,  21  engravings,  and2  full-page  plates.     Cloth,  $2.40,  net. 

HARRINGTON  (CHARLES).  A  TREATISE  ON  PRACTICAL  HYGIENE. 
Second  edition.  Handsome  octavo  of  755  pages,  with  113  engravings  and  12  plates  in 
colors  and  monochrome.     Cloth,  $4.25,  net. 

HARTSHORNE  (HENRY).  ANATOMY  AND  PHYSIOLOGY.  12mo.,  310 
pages,  with  220  engravings.     Cloth,  $1.75. 

A  CONSPECTUS  OF  THE  MEDICAL  SCIENCES.     Comprising  Manuals 

of  Anatomy,  Physiology,  Chemistry,  Materia  Medica,  Practice  of  Medicine,  Surgery  and 
Obstetrics.  Second  edition.  12mo.,  1028  pages,  with  477  illustrations.  Cloth,  $4.25; 
leather,  $5. 

HAYDEN  (JAMES  R.).  A  POCKET  TEXT-BOOK  OF  VENEREAL  DIS- 
EASES. Third  edition.  In  one  12mo.  volume  of  304  pages,  with  66  engravings. 
Cloth,  $1.75,  net.  ;  Flexible  red  leather,  $2.25,  net.  Lea's  Series  of  Pocket  Text-Books. 
Page  12. 

HAYEM  (GEORGES)  AND  HARE  (H.  A.).  PHYSICAL  AND  NATURAL 
THERAPEUTICS.  Heat,  Electricity,  Climate  and  Mineral  Waters.  Edited  by 
H.  A.  Hare,  M.D.     Octavo,  414  pages,  with  113  engravings.     Cloth,  $3. 

HERMAN  (G.  ERNEST).  FIRST  LINES  IN  MIDWIFERY.  12mo.,  198  pages, 
with  80  engravings.     Cloth,  $1.25.     See  Student^  Series  of  Manuals.     Page  15. 


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HERRICK  ( JAMES  B.j.     A  HANDBOOK  OP  DIAGNOSIS.     In  one  ban 
L2mo.  volume  of  429  pages,  wit  I ■  80  engraving    and  'j  colored  | 

HERTER    (C.  A.).      LECTURES    Oh    CHEMICAL    PATHOLOGY.     Inooi 
1 2  mo.  volume  of  46  I  page  i     Cloth      ;  •  ■.  net, 

HILL  (BERKELEY).    SYPHILIS  AND  LOCAL  CONTAGIOUS  Dl   OBI 

In  one  Svn.   volume  of    I  i '9  pOJ V  ■       Clotl 

HILLIER  (THOMAS).     A   HANDBOOK  OP  SKIN  DISEASES. 
In  one  royal  L2mo.  polumi  of  858  page    with  two  plat<       '  -  *  *  *  -' «   |2.26. 

HIRST  (BARTON  C.)  AND  PIERSOL    GEORGE  A.  >.     HUMAN   Hi 

[TIES.     Magnificent  folio, containing  220  pa  ind  ill"  trated  *itli  128  engrave 

Ings  and  89  large  photographic  plate   from  nature,     [n  four  pari  ,pria 

HOBLYN  (RICHARD  D.).  A  DIOTIONABY  OP  THE  TERM  V  ED  IN 
MEDICINE  AND   THE  COLL ATEBAL  SCIENCES.    Thirteenth  edition.     In 

one  L2mo.  volume  of  846  page  ,     Cloth,  ■'■'•  00,  net. 

HOLMES  (TIMOTHY).    A  TBEATISE  ON  SUBG1  BY.     Fifth  edition.    " 
1008  pages,  with  428  engravings.     Cloth,  $6;  leathei 

ASYSTEM  OFSUBGEBY.     Edited  byJoHa  II.  Packabd.  M.h.      In  three 

8vo.  volume*,  8187  pages,  (.'7:t  engravings,  18  plates.     Per  volume,  *  floth,  $6. 

HUNTINGTON  (GEORGE  S.).  ABDOMINAL  ANATOMY,  [mperial  quarto, 
590  pages,  including  800  full-page  plates.     De  luxe  edition,  (10.00, 

HYDE  (JAMES  NEVINS)  AND  MONTGOMERY  FRANK  H.  .  A  PBAC 
TIGAL  TREATISE  ON  DISEASES  OP  THE  SKIS.     Sixth  edition,  thoroughly 

revised.      Octavo,  832  pages,  with   107  engravings  and  27  full-page  plat*-,  9  of  which 
are  colored.     Cloth,  $4.50,  net;  leather,  $5. 50,  »<i  ;  half  morocco,  16.00, 

JACKSON  (  GEORGE  THOMAS ) .     THE  RE  A  D  Y-BEFEBENCE  HA  NDB  OOK 

OF  DISEASES  OF  THE  SKIN.     Fourth    edition.     12mo.    volume   of    617    pages, 
with  82  engravings,  and  3  colored  plates.     Cloth,  $2.75,  in  I. 

JAMIESON  (W.  ALLAN).  DISEASES  OF  THE  SKIN.  Third  edition.  Octavo, 
656  pages,  with  1  engraving  and  9  double-page  chromo-lithographic  plates.     Cloth,  $6. 

JEWETT  (CHARLES).  ESSENTIALS  OF  OBSTETRICS.  Second  edition. 
12mo.,  385  pages,  with  80  engravings  and  5  colored  plates.     Cloth,     .$2.25,  net. 

THE  PRACTICE  OF  OBSTETRICS.     By  American  Author?.    Second  edition. 

One    octavo  volume  of  775  pages,   with    445  engravings  in  black   and  colors,  and   35 
full-page  colored  plates.     Cloth,    $5.00;  leather,  $6.00;  half  morocco,  ••fG.  50. 

JULER  (HENRY).  A  HANDBOOK  OF  OPHTHALMIC  SCIENCE  AND 
PRACTICE.  Second  edition.  Octavo,  549  pages,  with  201  engravings,  17  chromo- 
lithographic  plates,  test-types  and  Color-Blindness  Test.     Cloth,  $5.50;   leather,  | 

KELLY  (A.O.J.)  A  MANUAL  OF  THE  PRACTICE  OF  MEDICINE. 
Octavo,  about  600  pages,  illustrated.     Preparing. 

KIRK    (EDWARD    C).       OPERATIVE  DENTISTRY.     Second    edition.       - 
American  Text-boote  of  Dentistry,  page  2. 

KING  (A.  F.  A.).  A  MANUAL  OF  OBSTETRICS.  Eighth  edition.  In  one 
12mo.  volume  of  612  pages,  with  264  illustrations.     Cloth,  $2.50.  net. 

KLEIN  (E.).     ELEMENTS  OF  HISTOLOGY.     Fifth  edition.     In  one  pocket-size 
12mo.   volume  of  506  pages,  with  296  engravings.     Cloth,  $2.00,  net.     Studeni     s 
Manuals.     Page  15. 

KOPLIK  (HENRY).  DISEASES  OF  INFANCY  AND  CHILDHOOD.  Octavo, 
675  paces  with  169  engravings  and  32  plates  in  black  and  colors.  Cloth,  (5.00  :  leather. 
$6.00,  net.     Just  Beady. 

KUSTNER  (OTTO)  AND  BEYEA  HENRY  D.  .  .4  TEXT-BOOK  OF  GYNE- 
COLOGY.    Octavo.  400  pages,  with  260  engravings.     Preparing. 


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LANDIS  (HENRY  G.).  THE  MANAGEMENT  OF  LABOR.  In  one  handsome 
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LA  ROCHE  (R.).  YELLOW  FEVER.  In  two  8vo.  volumes  of  1468  pages. 
Cloth,  $7. 

LEA  (HENRY  O.  CHAPTERS  FRO 31  THE  RELIGIOUS  HISTORY  OF 
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THE  ENDEMONIADAS ;  EL  SANTO  NINO  BE  LA  GUARBIA;  BRI- 
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A  HISTCRY  OF  AURICULAR  CONFESSION  ANB  INBULGENCES 

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THE  MORISCOS  OF  SPAIN :  THEIR  CONVERSION  ANB  EXPULSION. 

In  one  royal  12mo.  volume  of  about  425  pages.     Extra  cloth,  $2.25,  net. 

STUBIES   IN  CHURCH  HISTORY.      New    edition.      12mo.,    605  pages. 

Cloth,  $2.50. 

SUPERSTITION  ANB  FORCE;  ESSAYS  ON  THE  WAGER  OF  LAW, 

THE    WAGER    OF  BATTLE,   THE   ORBEAL   ANB    TORTURE.     Fourth 
edition,  thoroughly  revised.     In  one  royal  12mo.  volume  of  629  pages.     Cloth,  $2.75. 

LEA'S  SERIES  OF  MEDICAL  EPITOMES.  Covering  the  entire  field  of  medicine 
and  surgery  in  twenty  convenient  volumes  of  about  250  pages  each,  amply  illustrated 
and  written  by  prominent  teachers  and  specialists.  Compendious,  authoritative  and 
modern.  Following  each  chapter  is  a  series  of  questions  which  will  be  found  convenient 
in  quizzing.     The  Series  is  constituted  as  follows  : 

Hale's  Anatomy.  Guenther's  Physiology.  McGlannan's  Chemistry  and  Physics. 
Kiepe's  Materia  Medica  and  Therapeutics.  Dayton's  Practice  of  Medicine.  Hollis's 
Physical  Diagnosis.  Arneill's  Clinical  Diagnosis  and  Urinalysis.  Nagle's  Nervous  and 
Mental  Diseases.  Wathen's  Histology.  Stenhouse's  Pathology.  Archinard's  Bacteri- 
ology. Magee  and  Johnson's  Surgery.  Ailing,  Griflen  and  Ferguson's  Eye,  Ear,  Nose 
and  Throat.  Schmidt's  Genito-Urinary  and  Venereal  Diseases.  Schalek's  Dermatology. 
Pedersen's  Gynaecology.  Manton's  Obstetrics.  Tuley's  Pediatrics.  Dwight's  Jurispru- 
dence.    Dwight's  Toxicology. 

LEA'S  SERIES  OF  POCKET  TEXT-BOOKS.     See  page  12. 

LE  FEVRE  (EGBERT).  A  TEXT-BOOK  OF  PHYSICAL  BIAGNOSIS.  12mo., 
450  pages,  74  engravings,  12  plates.     Cloth,  $2.25,  net. 

LONG  (ELI).  BENTAL  MATERIA  MEBICA  ANB  THERAPEUTICS. 
12mo.,  321  pages,  6  engravings,  18  plates.     Cloth,  $3.00,  net. 

LOOMIS  (ALFRED  L.)  AND  THOMPSON  (W.  GILMAN),  Editors.  A  SYS- 
TEM OF  PRA  CTICAL  MEBICINE.  In  Contributions  by  Various  American  Authors. 
In  four  very  handsome  octavo  volumes  of  about  900  pages  each,  fully  illustrated  in  black 
and  colors.  Per  volume,  cloth,  $5 ;  leather,  $6 ;  half  Morocco,  $7.  For  sale  by  sub- 
scription only.     Full  prospectus  free  on   application. 

LYMAN  (HENRY  M.).  THE  PRACTICE  OF  MEBICINE.  In  one  very  hand- 
some octavo  volume  of  925  pages  with  170  engravings.     Cloth,  $4.75;  leather,  $5.75. 

MACKENZIE  (JOHN  NOLAND).  THE  BISEASES  OF  THE  NOSE  ANB 
THROAT.     Octavo,  of  about  600  pages,  richly  illustrated.     Preparing. 

MAISCH  (JOHN  M.).  A  MANUAL  OF  ORGANIC  MATERIA  MEBICA. 
Seventh  edition,  thoroughly  revised  by  H.  C.  C.  Maisch,  Ph.G.,  Ph.D.  In  one  12mo. 
of  512  pages,  with  285  engravings.     Cloth,  $2.50,  net. 

MALSBARY  (GEO.  E.).  A  POCKET  TEXT-BOOK  OF  THEORY  ANB 
PRACTICE  OF  MEBICINE.  12mo.  405  pages,  with  45  illustrations.  Cloth,  $1.75, 
net;  flexible  red  leather,  $2.25,  net.     Lea's  Series  of  Pocket  Text-Books.     Page  12. 


Philadelphia,  706,  708  and  710  Sansom  St.— New  York,  111  Fifth  Avenue. 


LEA     BROTHERS     &     CO.'S    PUBLICATIONS.  11 

MANTON  <W.  P.).     AN   EPITOME  OF  OBSTETRIC 
Illustrations.     Cloth,  $1.00   net,     Lea    8eri(    oj  Medical  Epil 

MANUALS.    See  Students'  Qui*  ■'••  >  14 ;   8tua\ 

Manuals,  page  18;  Medical  Epitorm  ,  page  L0     P 

MARSH  (HOWARD;.     DISEASES  OF  THE  JOINTS,     in  one  L2mo.  rola 

468  pages,  with  64  engraving    ana  b  colored  plate.    Cloth,  - 

Manuals,  page  18. 
MARTIN  (EDWARD.)    SUROIOAL    DIAGNOSIS.    One   L2mo.  •volume  o(   400 

pages,  richly  illustrated.     Prepo 

MARTIN  (WALTON)  AND  ROCKWELL  W.  II.,  JR.        I    POCK1 

BOOK   OF   CHEMISTRY    AND    I'll)  '.mo.  366  pages,  with   187  Illus- 

trations.   <  lloth,  $1.60,  net .  flea  Ible  leather,  I  ' 

Books.     Page  I  2. ' 

McOLANNAN  (A.),     yl  .v    EPITOME  \OF    OHEMI8TRY    AND    PHY 
12mo,  250  pages,  illustrated.     Cloth,  &1.00,  net      / 
page  l  <  >. 

MEDICAL  NEWS  POCKET  FORMULARY. 

MITCHELL   (JOHN  K.).     REMOTE  CONSEQUENCES  OF   INJUBIE 
NERVES  A  ND  THEIR  TREA  'I'M EST.    l2mo.,  239  pages,  12  illustrations.    I  loth, 
$1.75. 

MITCHELL  (S.  WEIR).     CLINICAL   LESSONS   ON   NERVOUS   DISE 
l2mo.,  299  pages,  with  17  engravings  and  2  colored  plates.     Cloth,  $2.50. 

MORRIS   (MALCOLM).    DISEASES  OF  THE  SKIN.    Second  edition.     12...... 

601   pages,  with  10  chromo-lithographic  plates  and  26  engravings.      Cloth,  $3.2-5,   net. 

MORROW  (PRINCE  A.).     THE  RELATIONS  OF  VENEREAL  DI8EA 
WITH  MARRIAGE.    Octavo,  about  450  page3,  with  many  illustrations.     Prep 

MULLER  (J.).  PRINCIPLES  OF  PHYSICS  AND  METEOROLOGY.  In  one 
large  8vo.  volume  of  623  pages,  with  538  engraving.     <  loth,  $4.50. 

MUSSER  (JOHN  H.).    A  TREATISE  ON  MEDICAL  DIAGNOSIS,  for  Students 

and  Physicians.     Fourth  edition.     Octavo,  1104  pages,  with  250  engravings  and  49  full- 
page  colored  plates.     Cloth,  $6.00;  leather,  $7.00;  half  morocco,  $750,  net 

NATIONAL  DISPENSATORY.     See  Stitte,  Maisch  &  Caspari,  page  14. 

NATIONAL    FORMULARY.      See  National  Dispensatory,  page  14. 

NATIONAL  MEDICAL  DICTIONARY.     See  Billings,  page  3. 

NETTLESHIP  (E.).  DISEASES  OF  THE  EYE.  Sixth  American  from  sixth 
English  edition.  Thoroughly  revised.  12mo. ,  562  pages,  with  192  engravings,  5  colored 
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NICHOLS  (JOHN  B.)  AND  VALE  (F.  P.).  A  POCKET  TEXT-BOOK  OF 
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NORRIS  (WM.  F.)  AND  OLIVER  (CHAS.  A.).  TEXT-BOOK  OF  OPHTHAL- 
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plates.     Cloth,  $5  ;  leather,  $6. 

OWEN  (EDMUND).  SURGICAL  DISEASES  OF  CHILDREN.  In  one  12nio. 
volume  of  525  pages,  with  85  engravings  and  4  colored  plates.     Cloth.  *2.     See  Series  of 

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PARK  (WILLIAM  H.).  BACTERIOLOGY  IN  MEDICINE  AND  SURGERY. 
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PARK  (ROSWELL\  Editor.  A  TREATISE  ON  SURGERY,  by  American  Authors. 
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2  colored  plates.     Cloth,  $4.25;  leather,  $5.25. 

PEPPER'S  SYSTEM  OF  MEDICINE.    See  page  2. 

PEPPER  (A.  J.).  SURGICAL  PATHOLOGY.  In  one  12mo  volume  of  511  pages, 
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PICK  (T.  PICKERING).  FRACTURES  AND  DISLOCATIONS.  In  one  12mo. 
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PLAYFAIR  (W.  S.).  THE  SCIENCE  AND  PRACTICE  OF  MIDWIFERY. 
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POLITZER  (ADAM).  A  TEXT-BOOK  OF  THE  DISEASES  OF  THE  EAR 
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In  one  octavo  volume  of  896  pages,  with  346  engravings.     Cloth,  $7.50,  net.    Just  Ready. 

POCKET  FORMULARY.     Fifth  edition.     See  page  1. 

POCKET  TEXT-BOOK  SERIES  covers  the  entire  domain  of  medicine  in  eighteen 
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leges. Issued  under  the  editorial  supervision  of  Bern  B.  Gallatjdet,  M.D. ,  of  the  College 
of  Physicians  and  Surgeons,  New  York.  Thoroughly  modern  and  authoritative,  concise 
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Obstetrics ;  Gynecology ;  Diseases  of  Children  ;  Bacteriology ;  Nursing ;  Massage. 
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A    TEXT-BOOK   ON   MEDICINE  AND   SURGICAL  ELECTRICITY. 

Octavo,  about  350  pages,  amply  illustrated.     Shortly. 

POSEY  (W.  C.)  AND  WRIGHT  (JONATHAN).  A  TREATISE  ON  THE 
EYE,  NOSE,  THROAT  AND  EAR.  Octavo,  1251  pages,  richly  illustrated  with 
650  engravings  and  35  plates  in  black  and  colors.  Cloth,  $7.00;  leather,  $8.00,  net. 
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net.     Vol.  II.,  Wright  on  the  Nose,  Throat  and  Ear.     Cloth,  $3.50,  net. 

PROGRESSIVE  MEDICINE.     See  page  1.     Per  annum,  $10.00. 

PURDY  (CHARLES  W.).  B RIGHT'S  DISEASE  AND  ALLIED  AFFEC- 
TIONS OF  THE  KIDNEY.  In  one  octavo  volume  of  288  pages,  with  18  engrav- 
ings.    Cloth,  $2. 

PYE-SMITH  (PHILIP  H.).  DISEASES  OF  THE  SKIN.  In  one  12mo.  volume 
of  407  pages,  with  28  illustrations,  18  of  which  are  colored.     Cloth,  $2. 

QUIZ  SERIES.     See  Students'  Quiz  Series,  page  14. 

RALFE  (CHARLES  H.).  CLINICAL  CHEMISTRY.  In  one  12mo.  volume  of 
314  pages,  with  16  engravings.     Cloth,  $1.50.     See  Students'  Series  of  Manuals,  page  14. 

REMSEN    (IRA).     THE  PRINCIPLES  OF  THEORETICAL    CHEMISTRY. 

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REYNOLDS  (EDWARD)  AND  NEWELL  (F.  S.).  MANUAL  OF  PRACTI- 
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RICHARDSON   (BENJAMIN   WARD).     PREVENTIVE  MEDICINE     In  oat 

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SCHAFER  (EDWARD  A. ).    77//<;  ESSENTIA  LS  OF  HISTOL06  P   /</.   (  /.//'- 
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lions.     ( Sloth,  $8,  net, 

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SCHALEK   (ALFRED).     AN    EPITOME    OF   DERMATOLOGY 

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SCHLEIF  iWM.).      A     POCKET    TEXT-BOOK    OF    MATERIA     MED 
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SCHMAUS  (HANS.)  AND  EWING  (JAMES).  PATHOLOGY  AND  PATH- 
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SCHMIDT  (LOUIS  E. ).    AN  EPITOME  OF  GEN  IT  O- I  'RIXA  R  Y  A  ND  VENE- 
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SCHREIBER  (JOSEPH).  A  MANUAL  OF  TREATMENT  BY  MASSAGE 
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SCOTT  (R.  J.  E. ).     See  State  Board  Examinations,  page  14. 

SENN  (NICHOLAS).     SURGICAL  BACTERIOLOGY.     Second  edition.     In  one 

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For  separate  notices,  see  under  various  authors'  names. 

SERIES  OF  POCKET  TEXT-BOOKS.     See  page  12. 

SERIES  OF  STATE  BOARD  EXAMINATIONS.     See  page  14. 

SERIES  OF  STUDENTS'  MANUALS.     See  page  15. 

SIMON  (CHARLES  E.\  CLINICAL  DIAGNOSIS,  BY  MICROSCOPICAL 
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SMITH  (J.  LEWIS).  THE  DISEASES  OF  INFANCY  AND  CHILDHOOD. 
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SMITH  (STEPHEN).  OPERATIVE  SURGERY.  Second  and  thoroughly  revised 
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SOLLY  (S.  EDWIN).  A  HANDBOOK  OF  MEDICAL  CLIMATOLOGY 
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STARR  iM.  ALLEN).  A  TREATISE  ON  ORGANIC  NERVOUS  DISEASES. 
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STATE  BOARD  EXAMINATION  SERIES.  Classified  and  Edited  by  R.  J.  E. 
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STILLE    (ALFRED),   MAISCH   (JOHN    M.)   AND   CASPARI   (CHAS.   JR.). 

THE  NATIONAL  DISPENSATORY :  Containing  the  Natural  History,  Chemistry, 
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gravings.   Cloth,  $7.25;  leather,  $8.     With  Thumb  Index.    Cloth,  $7.75;  leather,  $8.50. 

STIMSON  (LEWIS  A.).    A  MANUAL  OF  OPERATIVE  SURGERY.     Fourth 
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92.00;    Rales'    I  Unical  I  heml  ti 

For  separate  notice  ,   ee  under  variou   author  '  nan 

STUROES  (OCTAVIUSi.     AN  XNTBODUi  FIOA   TO  THE     VUDY  "I   <  . 
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SUTER  (W.  NORWOOD).     A    MANUAL  OF BEFB ACTIO      IND    WTILITY 

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SUTTON  (JOHN  BLAND).  8UBOICAL  DISEASES  OF  THE  OVARIES 
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SZYMONOWICZ  (L.)  AND  MacCALLUM  | J.  BRUCE  .      I    TEXT-BOOl 
HISTOLOGY  OF    THE   HUMAh    BODY:    including    Microscopical   Technique. 
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TAIT  (LAWSONV     DISEASES  OF  WOMEN  A  M>  A  BDOMINA  I.  8UBG  I 
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TAYLOR  (ALFRED  S.).  MEDICAL  JURISPRUDENCE.  Prom  the  twelfth 
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with  54  engravings  and  o  full-page  plates,     (loth,  $4.50;  leather,  $5.60. 

TAYLOR  (ROBERT  W.).  CENITO-URINARY  AND  VENEREAL  DIS- 
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and  27  colored  plates.     Cloth,  $5.00;  leather,  $6.00;  half  morocco,  $6.50. 

A  PRACTICAL  TREATISE  ON  SEXUAL  DISORDERS  LS  THE  MALE 

AND  FEMALE.       Second  edition.     Octavo,  434  pages,  with  91    engravings  and   13 
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A    CLINICAL    ATLAS    OF    VENEREAL    AND    SKIN     DISEASES. 


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TAYLOR  (SEYMOUR).  INDEX  OF  MEDICINE.  A  Manual  for  the  use  of  Senior 
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THOMAS  (T.  G-AILLARD)  AND  MUNDE  PAUL  P.).  A  PRACTICAL 
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revised.     Octavo  824,  pages,  with  347  engravings.     Cloth,  $5 ;  leather,  % 

THOMPSON  (W.GILMAN).  A  TEXT-BOOK  OF  PRACTKAL  MEDICINE, 
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tions.    Cloth,  $5.00,  leather,  $6.00,  half  morocco,  $6.50.  net     Just  Beady. 

THOMPSON  (SIR  HENRYS  THE  PATHOLOGY  AND  TREATMENT  OF 
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third  English  edition.    Octavo,  359  pages,  with  47  engravings  and  3  plates.    Cloth.  | 

TIRARD  (NESTOR).  MEDICAL  TREATMENT  OF  DISEASES  AND  SYMP- 
TOMS    Handsome  octavo  volume  of  627  pa?es.     Cloth,  $4.0''. 

TREVES  (FREDERICK).  OPERATIVE  SURGERY.  In  two  Svo.  volumes  con- 
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16  LEA     BROTHERS     &     C  0.' S    PUBLICATIONS. 


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TUTTLE  GEO.  M.).  .4  POCKET  TEXT-BOOK  OF  DISEASES  OF 
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